The present study investigated the effect of treatment with methanolic extracts of Yin- and Yang-Chinese tonifying herbs on concanavalin A (Con A)/lipopolysaccharide (LPS)-stimulated splenocyte proliferation (adaptive...The present study investigated the effect of treatment with methanolic extracts of Yin- and Yang-Chinese tonifying herbs on concanavalin A (Con A)/lipopolysaccharide (LPS)-stimulated splenocyte proliferation (adaptive immunity) and natural killer (NK) cell activity (innate immunity) in an ex vivo mouse model. The results indicated that while treatment with most Yin herbal extracts potentiated the Con A/LPS-stimulated splenocyte proliferation, only Yang (but not Yin) herbal extracts stimulated NK cell activity. The differential effects of Yin- and Yang-Chinese tonifying herbs on innate and adaptive immunity are consistent with the Chinese medicine theory which depicts the Yin and Yang functional components of Zheng Qi (vital energy), with the Yang component being responsible for the first line of defense against invading microorganisms (i.e., innate immunity) and the Yin oner serving as a follow-up defensive response (adaptive immunity).展开更多
Obesity-induced insulin resistance is the hallmark of metabolic syndrome,and chronic,low-grade tissue inflammation links obesity to insulin resistance through the activation of tissue-infiltrating immune cells.Current...Obesity-induced insulin resistance is the hallmark of metabolic syndrome,and chronic,low-grade tissue inflammation links obesity to insulin resistance through the activation of tissue-infiltrating immune cells.Current therapeutic approaches lack efficacy and immunomodulatory capacity.Thus,a new therapeutic approach is needed to prevent chronic inflammation and alleviate insulin resistance.Here,we synthesized a tetrahedral framework nucleic acid(tFNA)nanoparticle that carried resveratrol(RSV)to inhibit tissue inflammation and improve insulin sensitivity in obese mice.The prepared nanoparticles,namely tFNAs-RSV,possessed the characteristics of simple synthesis,stable properties,good water solubility,and superior biocompatibility.The tFNA-based delivery ameliorated the lability of RSV and enhanced its therapeutic efficacy.In high-fat diet(HFD)-fed mice,the administration of tFNAs-RSV ameliorated insulin resistance by alleviating inflammation status.tFNAs-RSV could reverse M1 phenotype macrophages in tissues to M2 phenotype macrophages.As for adaptive immunity,the prepared nanoparticles could repress the activation of Th1 and Th17 and promote Th2 and Treg,leading to the alleviation of insulin resistance.Furthermore,this study is the first to demonstrate that tFNAs,a nucleic acid material,possess immunomodulatory capacity.Collectively,our findings demonstrate that tFNAs-RSV alleviate insulin resistance and ameliorate inflammation in HFD mice,suggesting that nucleic acid materials or nucleic acid-based delivery systems may be a potential agent for the treatment of insulin resistance and obesity-related metabolic diseases.展开更多
Because of complexity and non-predictability of the tunnel surrounding rock, the problem with the determination of the physical and mechanical parameters of the surrounding rock has become a main obstacle to theoretic...Because of complexity and non-predictability of the tunnel surrounding rock, the problem with the determination of the physical and mechanical parameters of the surrounding rock has become a main obstacle to theoretical research and numerical analysis in tunnel engineering. During design, it is a frequent practice, therefore, to give recommended values by analog based on experience. It is a key point in current research to make use of the displacement back analytic method to comparatively accurately determine the parameters of the surrounding rock whereas artificial intelligence possesses an exceptionally strong capability of identifying, expressing and coping with such complex non-linear relationships. The parameters can be verified by searching the optimal network structure, using back analysis on measured data to search optimal parameters and performing direct computation of the obtained results. In the current paper, the direct analysis is performed with the biological emulation system and the software of Fast Lagrangian Analysis of Continua (FLAC3D. The high non-linearity, network reasoning and coupling ability of the neural network are employed. The output vector required of the training of the neural network is obtained with the numerical analysis software. And the overall space search is conducted by employing the Adaptive Immunity Algorithm. As a result, we are able to avoid the shortcoming that multiple parameters and optimized parameters are easy to fall into a local extremum. At the same time, the computing speed and efficiency are increased as well. Further, in the paper satisfactory conclusions are arrived at through the intelligent direct-back analysis on the monitored and measured data at the Erdaoya tunneling project. The results show that the physical and mechanical parameters obtained by the intelligent direct-back analysis proposed in the current paper have effectively improved the recommended values in the original prospecting data. This is of practical significance to the appraisal of stability and informationization design of the surrounding rock.展开更多
The tumor suppressor phosphatase and tensin homolog(PTEN)is a lipid and protein phosphatase that is able to antagonize the PI3K/AKT pathway and inhibit tumor growth.PTEN also possesses phosphatase-independent function...The tumor suppressor phosphatase and tensin homolog(PTEN)is a lipid and protein phosphatase that is able to antagonize the PI3K/AKT pathway and inhibit tumor growth.PTEN also possesses phosphatase-independent functions.Genetic alterations of PTEN may lead to the deregulation of cell proliferation,survival,differentiation,energy metabolism and cellular architecture and mobility.Although the role of PTEN in tumor suppression is extensively documented and well established,the evidence for its roles in immunity did not start to accumulate until recently.In this review,we will focus on the newly discovered functions of PTEN in the regulation of innate and adaptive immunity,including antiviral responses.展开更多
Acute-on-chronic hepatitis B liver failure(ACHBLF)is a term used to define the acute deterioration of liver function that occurs in patients with chronic hepatitis B virus infection or hepatitis B virus-related liver ...Acute-on-chronic hepatitis B liver failure(ACHBLF)is a term used to define the acute deterioration of liver function that occurs in patients with chronic hepatitis B virus infection or hepatitis B virus-related liver cirrhosis.The specific pathogenesis of ACHBLF is still not completely understood.Current research has shown that an intense systemic inflammation is involved in the development of acute-on-chronic liver failure(ACLF).Meanwhile,a subsequent immune paresis over the course of ACLF favors the development of infection and sepsis.Deregulation in both the innate and adaptive immunity is the notable feature of ACLF.The dysregulated immune responses play a crucial role in disease progression and potentially drive organ failure and mortality in ACHBLF.In this review,we highlight the current knowledge of innate and adaptive immune cells in ACHBLF.展开更多
Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the und...Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.展开更多
Mammalian T-cell responses require synergism between the first signal and co-stimulatory signal.However,whether and how dual signaling regulates the T-cell response in early vertebrates remains unknown.In the present ...Mammalian T-cell responses require synergism between the first signal and co-stimulatory signal.However,whether and how dual signaling regulates the T-cell response in early vertebrates remains unknown.In the present study,we discovered that the Nile tilapia(Oreochromis niloticus)encodes key components of the LAT signalosome,namely,LAT,ITK,GRB2,VAV1,SLP-76,GADS,and PLC-γ1.These components are evolutionarily conserved,and CD3εmAb-induced T-cell activation markedly increased their expression.Additionally,at least ITK,GRB2,and VAV1 were found to interact with LAT for signalosome formation.Downstream of the first signal,the NF-κB,MAPK/ERK,and PI3K-AKT pathways were activated upon CD3εmAb stimulation.Furthermore,treatment of lymphocytes with CD28 mAbs triggered the AKT-mTORC1 pathway downstream of the co-stimulatory signal.Combined CD3εand CD28 mAb stimulation enhanced ERK1/2 and S6 phosphorylation and elevated NFAT1,c-Fos,IL-2,CD122,and CD44 expression,thereby signifying T-cell activation.Moreover,rather than relying on the first or co-stimulatory signal alone,both signals were required for T-cell proliferation.Full T-cell activation was accompanied by marked apoptosis and cytotoxic responses.These findings suggest that tilapia relies on dual signaling to maintain an optimal T-cell response,providing a novel perspective for understanding the evolution of the adaptive immune system.展开更多
Chronic hepatitis B virus(HBV)infection is an international health problem with extremely high mortality and morbidity rates.Although current clinical chronic hepatitis B(CHB)treatment strategies can partly inhibit an...Chronic hepatitis B virus(HBV)infection is an international health problem with extremely high mortality and morbidity rates.Although current clinical chronic hepatitis B(CHB)treatment strategies can partly inhibit and eliminate HBV,viral breakthrough may result due to non-adherence to treatment,the emergence of viral resistance,and a long treatment cycle.Persistent CHB infection arises as a consequence of complex interactions between the virus and the host innate and adaptive immune systems.Therefore,understanding the immune escape mechanisms involved in persistent HBV infection is important for designing novel CHB treatment strategies to clear HBV and achieve long-lasting immune control.This review details the immunological and biological characteristics and escape mechanisms of HBV and the novel immune-based therapies that are currently used for treating HBV.展开更多
Picornaviruses, small positive-stranded RNA viruses, cause a wide range of diseases which is based on their differential tissue and cell type tropisms. This diversity is reflected by the immune responses, both innate ...Picornaviruses, small positive-stranded RNA viruses, cause a wide range of diseases which is based on their differential tissue and cell type tropisms. This diversity is reflected by the immune responses, both innate and adaptive, induced after infection, and the subsequent interactions of the viruses with the immune system. The defense mechanisms of the host and the countermeasures of the virus significantly contribute to the pathogenesis of the infections. Important human pathogens are poliovirus, coxsackievirus, human rhinovirus and hepatitis A virus. These viruses are the beststudied members of the family, and in this review we want to present the major aspects of the reciprocal effects between the immune system and these viruses.展开更多
Hepatitis C virus(HCV)infection affects about 170 million people worldwide and it is a major cause of liver cirrhosis and hepatocellular carcinoma.HCV is a hepatotropic non-cytopathic virus able to persist in a great ...Hepatitis C virus(HCV)infection affects about 170 million people worldwide and it is a major cause of liver cirrhosis and hepatocellular carcinoma.HCV is a hepatotropic non-cytopathic virus able to persist in a great percentage of infected hosts due to its ability to escape from the immune control.Liver damage and disease progression during HCV infection are driven by both viral and host factors.Specifically,adaptive immune response carries out an essential task in controllingnon-cytopathic viruses because of its ability to recognize infected cells and to destroy them by cytopathic mechanisms and to eliminate the virus by non-cytolytic machinery.HCV is able to impair this response by several means such as developing escape mutations in neutralizing antibodies and in T cell receptor viral epitope recognition sites and inducing HCV-specific cytotoxic T cell anergy and deletion.To impair HCV-specific T cell reactivity,HCV affects effector T cell regulation by modulating T helper and Treg response and by impairing the balance between positive and negative co-stimulatory molecules and between pro-and antiapoptotic proteins.In this review,the role of adaptive immune response in controlling HCV infection and the HCV mechanisms to evade this response are reviewed.展开更多
Allogeneic hematopoietic stem cell transplantation is a deterministic curative procedure for various hematologic disorders and congenital immunodeficiency.Despite its increased use,the mortality rate for patients unde...Allogeneic hematopoietic stem cell transplantation is a deterministic curative procedure for various hematologic disorders and congenital immunodeficiency.Despite its increased use,the mortality rate for patients undergoing this procedure remains high,mainly due to the perceived risk of exacerbating graft-versushost disease(GVHD).However,even with immunosuppressive agents,some patients still develop GVHD.Advanced mesenchymal stem/stromal cell(MSC)strategies have been proposed to achieve better therapeutic outcomes,given their immunosuppressive potential.However,the efficacy and trial designs have varied among the studies,and some research findings appear contradictory due to the challenges in characterizing the in vivo effects of MSCs.This review aims to provide real insights into this clinical entity,emphasizing diagnostic,and therapeutic considerations and generating pathophysiology hypotheses to identify research avenues.The indications and timing for the clinical application of MSCs are still subject to debate.展开更多
The ability of CD4 T cells to differentiate into various effector or regulatory T cell subsets explains the successful adaptation of immune responses to different types of infectious pathogens. Immune responses in the...The ability of CD4 T cells to differentiate into various effector or regulatory T cell subsets explains the successful adaptation of immune responses to different types of infectious pathogens. Immune responses in the context of cancer are also shaped by CD4 T cells, which can directly affect cancer prognosis in patients. While the proinflammatory mediator interleukin(IL)-1β was initially shown to enhance Th2 cell responses, recent findings support a predominant role of two other members of the IL-1 family, IL-18 and IL-33, on the production of Th1 and Th2-derived cytokines. In addition, IL-1β was found to profoundly affect the biology of two recently identified CD4 T cell subsets, Th17 and Th9 cells. IL-1β is critical for Th17 cell differentiation and it enhances the production of IL-9 and IL-21 by Th9 cells, thus increasing their anticancer properties. We will here review the mechanisms accounting for the ability of IL-1 cytokines to affect the differentiation of CD4 effector T cells with a focus on Th17 and Th9 cells. The physiopathological relevance of IL-1-driven effects on CD4 T cells will also be discussed.展开更多
The evolutionary emergence of an efficient immune system has a fundamental role in our survival against pathogenic attacks. Nevertheless, this same protective mechanism may also establish a negative consequence in the...The evolutionary emergence of an efficient immune system has a fundamental role in our survival against pathogenic attacks. Nevertheless, this same protective mechanism may also establish a negative consequence in the setting of disorders such as autoimmunity and transplant rejection. In light of the latter, although research has long uncovered main concepts of allogeneic recognition, immune rejection is still the main obstacle to long-term graft survival. Therefore, in order to define effective therapies that prolong graft viability, it is essential that we understand the underlying mediators and mechanisms that participate in transplant rejection. This multifaceted process is characterized by diverse cellular and humoral participants with innate and adaptive functions that can determine the type of rejection or promote graft acceptance. Although a number of mediators of graft recognition have been described in traditional immunology, recent studies indicate that defining rigid roles for certain immune cells and factors may be more complicated than originally conceived. Current research has also targeted specific cells and drugs that regulate immune activation and induce tolerance. This review will give a broad view of the most recent understanding of the allogeneic inflammatory/tolerogenic response and current insights into cellular and drug therapies that modulate immune activation that may prove to be useful in the induction of tolerance in the clinical setting.展开更多
Fungal keratitis(FK)is a refractory disease that poses a serious threat to vision,with common risk factors like eye trauma,contact lens wearing,topical corticosteroids and antibiotic abuse.Nowadays,topical and systemi...Fungal keratitis(FK)is a refractory disease that poses a serious threat to vision,with common risk factors like eye trauma,contact lens wearing,topical corticosteroids and antibiotic abuse.Nowadays,topical and systemic anti-fungal drugs and ocular surgeries are still the main therapeutic modalities.However,the pathogenesis of FK,especially the immunologic mechanism within it,has not yet been deeply clarified.A better understanding of the pathogenesis of FK is imperative for more effective therapies and prognosis.Meanwhile,the immune protection strategies are also urgently required to manage FK.This review highlights recent advances in the immunologic mechanism in the pathogenesis of FK,in hope of providing valuable reference information for more effective anti-fungal treatment.展开更多
With the exception of an extremely small number of cases caused by single gene mutations,most autoimmune diseases result from the complex interplay between environmental and genetic factors.In a nutshell,etiology of t...With the exception of an extremely small number of cases caused by single gene mutations,most autoimmune diseases result from the complex interplay between environmental and genetic factors.In a nutshell,etiology of the common autoimmune disorders is unknown in spite of progress elucidating certain effector cells and molecules responsible for pathologies associated with inflammatory and tissue damage.In recent years,population genetics approaches have greatly enriched our knowledge regarding genetic susceptibility of autoimmunity,providing us with a window of opportunities to comprehensively re-examine autoimmunity-associated genes and possible pathways.In this review,we aim to discuss etiology and pathogenesis of common autoimmune disorders from the perspective of human genetics.An overview of the genetic basis of autoimmunity is followed by3 chapters detailing susceptibility genes involved in innate immunity,adaptive immunity and inflammatory cell death processes respectively.With such attempts,we hope to expand the scope of thinking and bring attention to lesser appreciated molecules and pathways as important contributors of autoimmunity beyond the‘usual suspects’of a limited subset of validated therapeutic targets.展开更多
The adaptive arm of the immune system is crucial for appropriate antitumor immune responses.It is generally accepted that clusters of differentiation 4^(+)(CD4^(+))T cells,which mediate T helper(Th)1 immunity(type 1 i...The adaptive arm of the immune system is crucial for appropriate antitumor immune responses.It is generally accepted that clusters of differentiation 4^(+)(CD4^(+))T cells,which mediate T helper(Th)1 immunity(type 1 immunity),are the primary Th cell subtype associated with tumor elimination.In this review,we discuss evidence showing that antitumor immunity and better prognosis can be associated with distinct Th cell subtypes in experimental mouse models and humans,with a focus on Th2 cells.The aim of this review is to provide an overview and understanding of the mechanisms associated with different tumor outcomes in the face of immune responses by focusing on the(1)site of tumor development,(2)tumor properties(i.e.,tumor metabolism and cytokine receptor expression),and(3)type of immune response that the tumor initially escaped.Therefore,we discuss how low-tolerance organs,such as lungs and brains,might benefit from a less tissue-destructive immune response mediated by Th2 cells.In addition,Th2 cells antitumor effects can be independent of CD8^(+)T cells,which would circumvent some of the immune escape mechanisms that tumor cells possess,like low expression of major histocompatibility-I(MHC-I).Finally,this review aims to stimulate further studies on the role of Th2 cells in antitumor immunity and briefly discusses emerging treatment options.展开更多
The disease coronavirus disease 2019(COVID-19)is a severe respiratory illness that has emerged as a devastating health problem worldwide.The disease outcome is heterogeneous,and severity is likely dependent on the imm...The disease coronavirus disease 2019(COVID-19)is a severe respiratory illness that has emerged as a devastating health problem worldwide.The disease outcome is heterogeneous,and severity is likely dependent on the immunity of infected individuals and comorbidities.Although symptoms of the disease are primarily associated with respiratory problems,additional infection or failure of other vital organs are being reported.Emerging reports suggest a quite common co-existence of gastrointestinal(GI)tract symptoms in addition to respiratory symptoms in many COVID-19 patients,and some patients show just the GI symptoms.The possible cause of the GI symptoms could be due to direct infection of the epithelial cells of the gut,which is supported by the fact that(1)The intestinal epithelium expresses a high level of angiotensin-converting enzyme-2 and transmembrane protease serine 2 protein that are required for the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)entry into the cells;(2)About half of the severe COVID-19 patients show viral RNA in their feces and various parts of the GI tract;and(3)SARS-CoV-2 can directly infect gut epithelial cells in vitro(gut epithelial cells and organoids)and in vivo(rhesus monkey).The GI tract seems to be a site of active innate and adaptive immune responses to SARS-CoV-2 as clinically,stool samples of COVID-19 patients possess proinflammatory cytokines(interleukin 8),calprotectin(neutrophils activity),and immunoglobulin A antibodies.In addition to direct immune activation by the virus,impairment of GI epithelium integrity can evoke immune response under the influence of systemic cytokines,hypoxia,and changes in gut microbiota(dysbiosis)due to infection of the respiratory system,which is confirmed by the observation that not all of the GI symptomatic patients are viral RNA positive.This review comprehensively summarizes the possible GI immunomodulation by SARS-CoV-2 that could lead to GI symptoms,their association with disease severity,and potential therapeutic interventions.展开更多
Green tea and its bioactive components possess many health-promoting and disease-preventing benefits,especially anti-inflammatory,antioxidant,anticancer,and metabolic modulation effects with multi-target modes of acti...Green tea and its bioactive components possess many health-promoting and disease-preventing benefits,especially anti-inflammatory,antioxidant,anticancer,and metabolic modulation effects with multi-target modes of action.In contrast,the effects and mechanisms of tea and its components on the immune system are rarely reviewed.The study aimed to review the most potent compounds in tea that affect the immune systems and mechanisms associated with it.As a result of in vitro studies,animal models,and human trials,researchers have found that green tea extracts and compounds have the possibility of modulating the innate immune system,adaptive immune system,and intestinal immune system.In immune-related diseases,tea polyphenols are the most significant compounds that modify immune functions,though other compounds are being investigated and cannot be ruled out.The review provides a new perspective on how the immune-regulatory effects of tea and its components are exerted on immune systems,as well as how they affect the emergence and treatment of diseases.展开更多
Evolving data show a variable expression of clinical neurological manifestations in patients suffering with coronavirus disease 2019(COVID-19)from early disease onset.The most frequent symptoms and signs are fatigue,d...Evolving data show a variable expression of clinical neurological manifestations in patients suffering with coronavirus disease 2019(COVID-19)from early disease onset.The most frequent symptoms and signs are fatigue,dizziness,impaired consciousness,ageusia,anosmia,radicular pain,and headache,as well as others.Based on the high number of series of cases reported,there is evidence for the implication of the immune system in the pathological mechanism of COVID-19.Although the exact role of the immunological mechanism is not elucidated,two main mechanisms are suggested which implicate the direct effect of severe acute respiratory syndrome coronavirus 2 infection in the central nervous system and neuroinflammation.In the context of neurological manifestations associated with COVID-19,neuropsychiatric disorders show an exacerbation and are described by symptoms and signs such as depression,anxiety,mood alterations,psychosis,post-traumatic stress disorder,delirium,and cognitive impairment,which appear to be common in COVID-19 survivors.A worsened score on psychopathological measures is seen in those with a history of psychiatric comorbidities.We review the neuropsychiatric manifestations associated with COVID-19 and some critical aspects of the innate and adaptive immune system involved in mental health disorders occurring in COVID-19.展开更多
Organ transplant rejection(OTR)is a complex immune reaction involving multiple cells,and it determines graft survival and patient prognosis.At present,most transplant recipients are administered a combination of immun...Organ transplant rejection(OTR)is a complex immune reaction involving multiple cells,and it determines graft survival and patient prognosis.At present,most transplant recipients are administered a combination of immunosuppressive and biological agents to protect them from OTR.However,immunosuppressive agents negatively impact the immune system of the patients,causing them to suffer from serious complications,such as chronic infection and malignant tumors.Therefore,a thorough understanding of the mechanisms involved in immune tolerance and immune rejection with regard to organ transplant(OT)is essential for developing better treatment options and improving patient outcomes.This article reviews the role of immune cells in OTR and organ transplant tolerance(OTT),including the novel cell therapies that are currently under clinical trials for transplant recipients.展开更多
文摘The present study investigated the effect of treatment with methanolic extracts of Yin- and Yang-Chinese tonifying herbs on concanavalin A (Con A)/lipopolysaccharide (LPS)-stimulated splenocyte proliferation (adaptive immunity) and natural killer (NK) cell activity (innate immunity) in an ex vivo mouse model. The results indicated that while treatment with most Yin herbal extracts potentiated the Con A/LPS-stimulated splenocyte proliferation, only Yang (but not Yin) herbal extracts stimulated NK cell activity. The differential effects of Yin- and Yang-Chinese tonifying herbs on innate and adaptive immunity are consistent with the Chinese medicine theory which depicts the Yin and Yang functional components of Zheng Qi (vital energy), with the Yang component being responsible for the first line of defense against invading microorganisms (i.e., innate immunity) and the Yin oner serving as a follow-up defensive response (adaptive immunity).
基金National Key R&D Program of China(2019YFA0110600)National Natural Science Foundation of China(81970916,81671031)the LU JIAXI International team program supported by the K.C.Wong Education Foundation and CAS and the Youth Innovation Promotion Association of CAS(Grant No.2016236).
文摘Obesity-induced insulin resistance is the hallmark of metabolic syndrome,and chronic,low-grade tissue inflammation links obesity to insulin resistance through the activation of tissue-infiltrating immune cells.Current therapeutic approaches lack efficacy and immunomodulatory capacity.Thus,a new therapeutic approach is needed to prevent chronic inflammation and alleviate insulin resistance.Here,we synthesized a tetrahedral framework nucleic acid(tFNA)nanoparticle that carried resveratrol(RSV)to inhibit tissue inflammation and improve insulin sensitivity in obese mice.The prepared nanoparticles,namely tFNAs-RSV,possessed the characteristics of simple synthesis,stable properties,good water solubility,and superior biocompatibility.The tFNA-based delivery ameliorated the lability of RSV and enhanced its therapeutic efficacy.In high-fat diet(HFD)-fed mice,the administration of tFNAs-RSV ameliorated insulin resistance by alleviating inflammation status.tFNAs-RSV could reverse M1 phenotype macrophages in tissues to M2 phenotype macrophages.As for adaptive immunity,the prepared nanoparticles could repress the activation of Th1 and Th17 and promote Th2 and Treg,leading to the alleviation of insulin resistance.Furthermore,this study is the first to demonstrate that tFNAs,a nucleic acid material,possess immunomodulatory capacity.Collectively,our findings demonstrate that tFNAs-RSV alleviate insulin resistance and ameliorate inflammation in HFD mice,suggesting that nucleic acid materials or nucleic acid-based delivery systems may be a potential agent for the treatment of insulin resistance and obesity-related metabolic diseases.
基金supported by the National Natural Science Foundation of China (No.50609028)
文摘Because of complexity and non-predictability of the tunnel surrounding rock, the problem with the determination of the physical and mechanical parameters of the surrounding rock has become a main obstacle to theoretical research and numerical analysis in tunnel engineering. During design, it is a frequent practice, therefore, to give recommended values by analog based on experience. It is a key point in current research to make use of the displacement back analytic method to comparatively accurately determine the parameters of the surrounding rock whereas artificial intelligence possesses an exceptionally strong capability of identifying, expressing and coping with such complex non-linear relationships. The parameters can be verified by searching the optimal network structure, using back analysis on measured data to search optimal parameters and performing direct computation of the obtained results. In the current paper, the direct analysis is performed with the biological emulation system and the software of Fast Lagrangian Analysis of Continua (FLAC3D. The high non-linearity, network reasoning and coupling ability of the neural network are employed. The output vector required of the training of the neural network is obtained with the numerical analysis software. And the overall space search is conducted by employing the Adaptive Immunity Algorithm. As a result, we are able to avoid the shortcoming that multiple parameters and optimized parameters are easy to fall into a local extremum. At the same time, the computing speed and efficiency are increased as well. Further, in the paper satisfactory conclusions are arrived at through the intelligent direct-back analysis on the monitored and measured data at the Erdaoya tunneling project. The results show that the physical and mechanical parameters obtained by the intelligent direct-back analysis proposed in the current paper have effectively improved the recommended values in the original prospecting data. This is of practical significance to the appraisal of stability and informationization design of the surrounding rock.
基金the financial support provided by the National Natural Science Foundation of China(81620108020 and 31300609)Hubei Province’s Outstanding Medical Academic Leader Program and Innovation Team(2015CFA009 to DG).
文摘The tumor suppressor phosphatase and tensin homolog(PTEN)is a lipid and protein phosphatase that is able to antagonize the PI3K/AKT pathway and inhibit tumor growth.PTEN also possesses phosphatase-independent functions.Genetic alterations of PTEN may lead to the deregulation of cell proliferation,survival,differentiation,energy metabolism and cellular architecture and mobility.Although the role of PTEN in tumor suppression is extensively documented and well established,the evidence for its roles in immunity did not start to accumulate until recently.In this review,we will focus on the newly discovered functions of PTEN in the regulation of innate and adaptive immunity,including antiviral responses.
基金This work was supported by the National Natural Science Foundation of China(No.81970522,No.82000564)Shandong University multidisciplinary research and innovation team of young scholars(2020QNQT11)+2 种基金Shandong Provincial Natural Science Foundation(ZR2019PH027)China Postdoctoral Science Foundation(2020M672074)the Young Taishan Scholars(tsqn202103169).
文摘Acute-on-chronic hepatitis B liver failure(ACHBLF)is a term used to define the acute deterioration of liver function that occurs in patients with chronic hepatitis B virus infection or hepatitis B virus-related liver cirrhosis.The specific pathogenesis of ACHBLF is still not completely understood.Current research has shown that an intense systemic inflammation is involved in the development of acute-on-chronic liver failure(ACLF).Meanwhile,a subsequent immune paresis over the course of ACLF favors the development of infection and sepsis.Deregulation in both the innate and adaptive immunity is the notable feature of ACLF.The dysregulated immune responses play a crucial role in disease progression and potentially drive organ failure and mortality in ACHBLF.In this review,we highlight the current knowledge of innate and adaptive immune cells in ACHBLF.
基金funded by the Spanish Ministry of Economy and Competitiveness,No.PID(2019)-106498GB-100 (to MVS)by the Instituto de Salud CarlosⅢ,Fondo Europeo de Desarrollo Regional"Una manera de hacer Europa",No.PI19/00071 (to MAB)+2 种基金the RETICS subprograms of Spanish Networks OftoRed,Nos.RD16/0008/0026 (to DGB) and RD16/0008/0016 (to DGB)RICORS Terav,No.RD16/0011/0001 (to DGB)from Instituto de Salud CarlosⅢby the Fundacion Seneca,Agencia de Cienciay Tecnologia Región de Murcia,No.19881/GERM/15 (all to MVS)
文摘Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.
基金supported by the National Key Research and Development Program(2022YFD2400804)National Natural Science Foundation of China(32022086,31972822)Natural Science Foundation of Shanghai(20ZR1417500)。
文摘Mammalian T-cell responses require synergism between the first signal and co-stimulatory signal.However,whether and how dual signaling regulates the T-cell response in early vertebrates remains unknown.In the present study,we discovered that the Nile tilapia(Oreochromis niloticus)encodes key components of the LAT signalosome,namely,LAT,ITK,GRB2,VAV1,SLP-76,GADS,and PLC-γ1.These components are evolutionarily conserved,and CD3εmAb-induced T-cell activation markedly increased their expression.Additionally,at least ITK,GRB2,and VAV1 were found to interact with LAT for signalosome formation.Downstream of the first signal,the NF-κB,MAPK/ERK,and PI3K-AKT pathways were activated upon CD3εmAb stimulation.Furthermore,treatment of lymphocytes with CD28 mAbs triggered the AKT-mTORC1 pathway downstream of the co-stimulatory signal.Combined CD3εand CD28 mAb stimulation enhanced ERK1/2 and S6 phosphorylation and elevated NFAT1,c-Fos,IL-2,CD122,and CD44 expression,thereby signifying T-cell activation.Moreover,rather than relying on the first or co-stimulatory signal alone,both signals were required for T-cell proliferation.Full T-cell activation was accompanied by marked apoptosis and cytotoxic responses.These findings suggest that tilapia relies on dual signaling to maintain an optimal T-cell response,providing a novel perspective for understanding the evolution of the adaptive immune system.
基金Supported by National Science Foundation for Young Scientists of China, No.82001687National Major Science and Technology Project for Control and Prevention of Major Infectious Diseases, No.2018ZX10301401+2 种基金National Postdoctoral Program for Innovative Talents, No.BX20190192China Postdoctoral Science Foundation, No.2020M672064National Basic Research Program of China, No.2013CB531503
文摘Chronic hepatitis B virus(HBV)infection is an international health problem with extremely high mortality and morbidity rates.Although current clinical chronic hepatitis B(CHB)treatment strategies can partly inhibit and eliminate HBV,viral breakthrough may result due to non-adherence to treatment,the emergence of viral resistance,and a long treatment cycle.Persistent CHB infection arises as a consequence of complex interactions between the virus and the host innate and adaptive immune systems.Therefore,understanding the immune escape mechanisms involved in persistent HBV infection is important for designing novel CHB treatment strategies to clear HBV and achieve long-lasting immune control.This review details the immunological and biological characteristics and escape mechanisms of HBV and the novel immune-based therapies that are currently used for treating HBV.
基金Supported by The Tonjes-Vagt-Stiftung,Bremen,Germany.
文摘Picornaviruses, small positive-stranded RNA viruses, cause a wide range of diseases which is based on their differential tissue and cell type tropisms. This diversity is reflected by the immune responses, both innate and adaptive, induced after infection, and the subsequent interactions of the viruses with the immune system. The defense mechanisms of the host and the countermeasures of the virus significantly contribute to the pathogenesis of the infections. Important human pathogens are poliovirus, coxsackievirus, human rhinovirus and hepatitis A virus. These viruses are the beststudied members of the family, and in this review we want to present the major aspects of the reciprocal effects between the immune system and these viruses.
基金Grants from"Instituto de Salud Carlos Ⅲ",Spain and"European Regional Development Fund(ERDF),a way of making Europe",E.U.,No.PI12/00130"Fundacion de In-vestigacion Medica Mutua Madrilena",Spain,No.8922/2011Lokhande MU was funded by a research grant from"Asoci-acion de Hepatologia Translacional"No.AHT-2010/01,Spain
文摘Hepatitis C virus(HCV)infection affects about 170 million people worldwide and it is a major cause of liver cirrhosis and hepatocellular carcinoma.HCV is a hepatotropic non-cytopathic virus able to persist in a great percentage of infected hosts due to its ability to escape from the immune control.Liver damage and disease progression during HCV infection are driven by both viral and host factors.Specifically,adaptive immune response carries out an essential task in controllingnon-cytopathic viruses because of its ability to recognize infected cells and to destroy them by cytopathic mechanisms and to eliminate the virus by non-cytolytic machinery.HCV is able to impair this response by several means such as developing escape mutations in neutralizing antibodies and in T cell receptor viral epitope recognition sites and inducing HCV-specific cytotoxic T cell anergy and deletion.To impair HCV-specific T cell reactivity,HCV affects effector T cell regulation by modulating T helper and Treg response and by impairing the balance between positive and negative co-stimulatory molecules and between pro-and antiapoptotic proteins.In this review,the role of adaptive immune response in controlling HCV infection and the HCV mechanisms to evade this response are reviewed.
文摘Allogeneic hematopoietic stem cell transplantation is a deterministic curative procedure for various hematologic disorders and congenital immunodeficiency.Despite its increased use,the mortality rate for patients undergoing this procedure remains high,mainly due to the perceived risk of exacerbating graft-versushost disease(GVHD).However,even with immunosuppressive agents,some patients still develop GVHD.Advanced mesenchymal stem/stromal cell(MSC)strategies have been proposed to achieve better therapeutic outcomes,given their immunosuppressive potential.However,the efficacy and trial designs have varied among the studies,and some research findings appear contradictory due to the challenges in characterizing the in vivo effects of MSCs.This review aims to provide real insights into this clinical entity,emphasizing diagnostic,and therapeutic considerations and generating pathophysiology hypotheses to identify research avenues.The indications and timing for the clinical application of MSCs are still subject to debate.
基金Supported by Fondation de France (to Apetoh L and Rivera Vargas T)the Association pour la recherche sur le cancer (to Apetoh L)+6 种基金the Institut Mérieux (to Apetoh L)the Conseil Régional de Bourgogne (to Apetoh L)the FEDER,the Agence Nationale de la Recherche,No.ANR-13-JSV3-0001 (to Apetoh L) and No.ANR-11-LABX-0021the ARSEP (to Apetoh L)the Ligue Régionale contre le cancer Comité Grand-Est (to Apetoh L)the European Commission (Marie Curie Fellowship PCIG10-GA-2011-303719)the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No.677251)
文摘The ability of CD4 T cells to differentiate into various effector or regulatory T cell subsets explains the successful adaptation of immune responses to different types of infectious pathogens. Immune responses in the context of cancer are also shaped by CD4 T cells, which can directly affect cancer prognosis in patients. While the proinflammatory mediator interleukin(IL)-1β was initially shown to enhance Th2 cell responses, recent findings support a predominant role of two other members of the IL-1 family, IL-18 and IL-33, on the production of Th1 and Th2-derived cytokines. In addition, IL-1β was found to profoundly affect the biology of two recently identified CD4 T cell subsets, Th17 and Th9 cells. IL-1β is critical for Th17 cell differentiation and it enhances the production of IL-9 and IL-21 by Th9 cells, thus increasing their anticancer properties. We will here review the mechanisms accounting for the ability of IL-1 cytokines to affect the differentiation of CD4 effector T cells with a focus on Th17 and Th9 cells. The physiopathological relevance of IL-1-driven effects on CD4 T cells will also be discussed.
基金Supported by Sao Paulo Research Foundation-FAPESP,Nos.2012/23347-3,2014/14147-6,2012/02270-2 and CNPq
文摘The evolutionary emergence of an efficient immune system has a fundamental role in our survival against pathogenic attacks. Nevertheless, this same protective mechanism may also establish a negative consequence in the setting of disorders such as autoimmunity and transplant rejection. In light of the latter, although research has long uncovered main concepts of allogeneic recognition, immune rejection is still the main obstacle to long-term graft survival. Therefore, in order to define effective therapies that prolong graft viability, it is essential that we understand the underlying mediators and mechanisms that participate in transplant rejection. This multifaceted process is characterized by diverse cellular and humoral participants with innate and adaptive functions that can determine the type of rejection or promote graft acceptance. Although a number of mediators of graft recognition have been described in traditional immunology, recent studies indicate that defining rigid roles for certain immune cells and factors may be more complicated than originally conceived. Current research has also targeted specific cells and drugs that regulate immune activation and induce tolerance. This review will give a broad view of the most recent understanding of the allogeneic inflammatory/tolerogenic response and current insights into cellular and drug therapies that modulate immune activation that may prove to be useful in the induction of tolerance in the clinical setting.
基金Supported by the Natural Science Foundation of Tianjin(No.19JCYBJC25700)Clinical Key Discipline(Specialty)Construction Project of Tianjin(No.TJLCZDXKM002)+1 种基金Science and Technology Projects of Social Development of Tianjin Binhai New District(No.BHXQKJXM-SF-2018-05)Science and Technology Projects of Health Commission of Tianjin Binhai New District(No.2019BWKZ008)。
文摘Fungal keratitis(FK)is a refractory disease that poses a serious threat to vision,with common risk factors like eye trauma,contact lens wearing,topical corticosteroids and antibiotic abuse.Nowadays,topical and systemic anti-fungal drugs and ocular surgeries are still the main therapeutic modalities.However,the pathogenesis of FK,especially the immunologic mechanism within it,has not yet been deeply clarified.A better understanding of the pathogenesis of FK is imperative for more effective therapies and prognosis.Meanwhile,the immune protection strategies are also urgently required to manage FK.This review highlights recent advances in the immunologic mechanism in the pathogenesis of FK,in hope of providing valuable reference information for more effective anti-fungal treatment.
文摘With the exception of an extremely small number of cases caused by single gene mutations,most autoimmune diseases result from the complex interplay between environmental and genetic factors.In a nutshell,etiology of the common autoimmune disorders is unknown in spite of progress elucidating certain effector cells and molecules responsible for pathologies associated with inflammatory and tissue damage.In recent years,population genetics approaches have greatly enriched our knowledge regarding genetic susceptibility of autoimmunity,providing us with a window of opportunities to comprehensively re-examine autoimmunity-associated genes and possible pathways.In this review,we aim to discuss etiology and pathogenesis of common autoimmune disorders from the perspective of human genetics.An overview of the genetic basis of autoimmunity is followed by3 chapters detailing susceptibility genes involved in innate immunity,adaptive immunity and inflammatory cell death processes respectively.With such attempts,we hope to expand the scope of thinking and bring attention to lesser appreciated molecules and pathways as important contributors of autoimmunity beyond the‘usual suspects’of a limited subset of validated therapeutic targets.
基金This work was supported by Coordination for the Improvement of Higher Education Personnel(CAPES),Carlos Chagas Filho Foundation for Supporting Research in the State of Rio de Janeiro(grant number FAPERJ E−26/200.628/2022)National Counsel of Technological and Scientific Development(CNPq)Brazil.
文摘The adaptive arm of the immune system is crucial for appropriate antitumor immune responses.It is generally accepted that clusters of differentiation 4^(+)(CD4^(+))T cells,which mediate T helper(Th)1 immunity(type 1 immunity),are the primary Th cell subtype associated with tumor elimination.In this review,we discuss evidence showing that antitumor immunity and better prognosis can be associated with distinct Th cell subtypes in experimental mouse models and humans,with a focus on Th2 cells.The aim of this review is to provide an overview and understanding of the mechanisms associated with different tumor outcomes in the face of immune responses by focusing on the(1)site of tumor development,(2)tumor properties(i.e.,tumor metabolism and cytokine receptor expression),and(3)type of immune response that the tumor initially escaped.Therefore,we discuss how low-tolerance organs,such as lungs and brains,might benefit from a less tissue-destructive immune response mediated by Th2 cells.In addition,Th2 cells antitumor effects can be independent of CD8^(+)T cells,which would circumvent some of the immune escape mechanisms that tumor cells possess,like low expression of major histocompatibility-I(MHC-I).Finally,this review aims to stimulate further studies on the role of Th2 cells in antitumor immunity and briefly discusses emerging treatment options.
文摘The disease coronavirus disease 2019(COVID-19)is a severe respiratory illness that has emerged as a devastating health problem worldwide.The disease outcome is heterogeneous,and severity is likely dependent on the immunity of infected individuals and comorbidities.Although symptoms of the disease are primarily associated with respiratory problems,additional infection or failure of other vital organs are being reported.Emerging reports suggest a quite common co-existence of gastrointestinal(GI)tract symptoms in addition to respiratory symptoms in many COVID-19 patients,and some patients show just the GI symptoms.The possible cause of the GI symptoms could be due to direct infection of the epithelial cells of the gut,which is supported by the fact that(1)The intestinal epithelium expresses a high level of angiotensin-converting enzyme-2 and transmembrane protease serine 2 protein that are required for the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)entry into the cells;(2)About half of the severe COVID-19 patients show viral RNA in their feces and various parts of the GI tract;and(3)SARS-CoV-2 can directly infect gut epithelial cells in vitro(gut epithelial cells and organoids)and in vivo(rhesus monkey).The GI tract seems to be a site of active innate and adaptive immune responses to SARS-CoV-2 as clinically,stool samples of COVID-19 patients possess proinflammatory cytokines(interleukin 8),calprotectin(neutrophils activity),and immunoglobulin A antibodies.In addition to direct immune activation by the virus,impairment of GI epithelium integrity can evoke immune response under the influence of systemic cytokines,hypoxia,and changes in gut microbiota(dysbiosis)due to infection of the respiratory system,which is confirmed by the observation that not all of the GI symptomatic patients are viral RNA positive.This review comprehensively summarizes the possible GI immunomodulation by SARS-CoV-2 that could lead to GI symptoms,their association with disease severity,and potential therapeutic interventions.
基金supported by College Student Innovation and Entrepreneurship Training(202110069122)Tianjin Key R&D Plan-Key Projects Supported by Science and Technology(19YFZCSN00010)Tianjin Agricultural Science and Technology Achievements Transformation and Promotion Project(202101120)。
文摘Green tea and its bioactive components possess many health-promoting and disease-preventing benefits,especially anti-inflammatory,antioxidant,anticancer,and metabolic modulation effects with multi-target modes of action.In contrast,the effects and mechanisms of tea and its components on the immune system are rarely reviewed.The study aimed to review the most potent compounds in tea that affect the immune systems and mechanisms associated with it.As a result of in vitro studies,animal models,and human trials,researchers have found that green tea extracts and compounds have the possibility of modulating the innate immune system,adaptive immune system,and intestinal immune system.In immune-related diseases,tea polyphenols are the most significant compounds that modify immune functions,though other compounds are being investigated and cannot be ruled out.The review provides a new perspective on how the immune-regulatory effects of tea and its components are exerted on immune systems,as well as how they affect the emergence and treatment of diseases.
文摘Evolving data show a variable expression of clinical neurological manifestations in patients suffering with coronavirus disease 2019(COVID-19)from early disease onset.The most frequent symptoms and signs are fatigue,dizziness,impaired consciousness,ageusia,anosmia,radicular pain,and headache,as well as others.Based on the high number of series of cases reported,there is evidence for the implication of the immune system in the pathological mechanism of COVID-19.Although the exact role of the immunological mechanism is not elucidated,two main mechanisms are suggested which implicate the direct effect of severe acute respiratory syndrome coronavirus 2 infection in the central nervous system and neuroinflammation.In the context of neurological manifestations associated with COVID-19,neuropsychiatric disorders show an exacerbation and are described by symptoms and signs such as depression,anxiety,mood alterations,psychosis,post-traumatic stress disorder,delirium,and cognitive impairment,which appear to be common in COVID-19 survivors.A worsened score on psychopathological measures is seen in those with a history of psychiatric comorbidities.We review the neuropsychiatric manifestations associated with COVID-19 and some critical aspects of the innate and adaptive immune system involved in mental health disorders occurring in COVID-19.
基金supported by grants from the National Natural Science Foundation of China(81971495 and 91442117)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-035)+2 种基金the National Science Foundation of Jiangsu Province(BRA2017533 and BK20191490)the State Key Laboratory of Reproductive Medicine(SKLRM-K202001)the Foundation of Jiangsu Collaborative Innovation Center of Biomedical Functional Materials。
文摘Organ transplant rejection(OTR)is a complex immune reaction involving multiple cells,and it determines graft survival and patient prognosis.At present,most transplant recipients are administered a combination of immunosuppressive and biological agents to protect them from OTR.However,immunosuppressive agents negatively impact the immune system of the patients,causing them to suffer from serious complications,such as chronic infection and malignant tumors.Therefore,a thorough understanding of the mechanisms involved in immune tolerance and immune rejection with regard to organ transplant(OT)is essential for developing better treatment options and improving patient outcomes.This article reviews the role of immune cells in OTR and organ transplant tolerance(OTT),including the novel cell therapies that are currently under clinical trials for transplant recipients.
