In order to analyze the mechanism of immunomodulation by LPS on murine peritoneal suppressor macrophages, we have, using RNase protection assay,checked the changes of mRNA expression pattern of several cytokine genes ...In order to analyze the mechanism of immunomodulation by LPS on murine peritoneal suppressor macrophages, we have, using RNase protection assay,checked the changes of mRNA expression pattern of several cytokine genes during the immuno-modulation.It has been found that, after treating peritoneal suppressor macrophages with LPS, mRNAs of IL-12 p35, IL-12 p40,IL-6 and IFN-γ are newly appeared, while those of IL-1α, IL-1β and IL-1Ra are increased and those of other cytokines, like TGF-β1 and MIF are not changed at all.It seems certain that those cytokines, whose expression is increased by LPS stimulation, may be responsible for the functional changes of suppressor macrophages during immuno-modulation. Among these changes, the appearance of IL-12 mRNA may play a critical role, and, in this regard, the synergetic effect between IFN-γ and LPS on the increase of IL-12 p35 and IL-12 p40 mRNA expression is an interesting finding.展开更多
Objective To investigate the effects of estrogen(E_2)level on regulatory T cells(Treg)in peripheral blood during pregnancy.Methods:A total of 30 healthy non-pregnant women were selected as control group,90 pregnant wo...Objective To investigate the effects of estrogen(E_2)level on regulatory T cells(Treg)in peripheral blood during pregnancy.Methods:A total of 30 healthy non-pregnant women were selected as control group,90 pregnant women of early,middle and late pregnancy and 30 postpartum women at 1 month after parturition were selected as experimental groups including early pregnancy group,middle pregnancy group and late pregnancy group;the proportions of CD4^+CD25^+Treg and CD4^+CD25^+CD127^-Treg among CD4 T cells were detected by flow cytometry;the serum estrogen content in peripheral blood was detected by electrochemical immune luminescence method.Results:E_2 level was coincident with the change of Tregs number during pregnancy.The estrogen content in peripheral blood increased gradually from early pregnancy to late pregnancy,then decreased significantly after parturition,and the level at 1 month after parturition down to the level in non-pregnancy group(P>0.05);the level of E_2 in pregnancy groups were significantly higher than those in non-pregnancy group(P<0.01);and there were significant differences among early pregnancy group,middle pregnancy group and late pregnancy group(P<0.05).The proportions of CD4^+CD25^+Treg and CD4^+CD25^+CD127^-Treg in pregnancy groups were significantly higher than those in non-pregnancy group(P<0.05),but decreased significantly after parturition,and there was no significant difference between non-pregnancy group and postpartum women group(P>0.05):the proportions in middle and late pregnancy groups were significantly higher than those in early pregnancy group(P<0.05).but decreased slightly in late pregnancy group,there was no significant difference between late pregnancy group and middle pregnancy group(P>0.05).There was correlation between Tregs number with estrogen level during pregnancy.The proportion of CD4^+CD25^+Treg and CD4^+CD25^+CD 127^-Treg were positively correlated with estrogen level.Conclusions:High proportion of CD4^+CD25^+Trcg and CD4^+CD25^+CD127^-Treg is closely related to the high level of E,during pregnancy.It suggested that high level of estrogen may induce an increase of CD4^+CD25^+Treg in peripheral blood.and then influence the immune function of pregnant women.The results of this experiment might play an important role of estrogen in immune-modulation during pregnancy.展开更多
Inflammatory bowel disease(IBD)is a common and lifelong disabling gastrointestinal disease.Emerging treatments are being developed to target inflammatory cytokines which initiate and perpetuate the immune response.Ade...Inflammatory bowel disease(IBD)is a common and lifelong disabling gastrointestinal disease.Emerging treatments are being developed to target inflammatory cytokines which initiate and perpetuate the immune response.Adenosine is an important modulator of inflammation and its anti-inflammatory effects have been well established in humans as well as in animal models.High extracellular adenosine suppresses and resolves chronic inflammation in IBD models.High extracellular adenosine levels could be achieved by enhanced adenosine absorption and increased de novo synthesis.Increased adenosine concentration leads to activation of the A2a receptor on the cell surface of immune and epithelial cells that would be a potential therapeutic target for chronic intestinal inflammation. Adenosine is transported via concentrative nucleoside transporter and equilibrative nucleoside transporter transporters that are localized in apical and basolateral membranes of intestinal epithelial cells,respectively. Increased extracellular adenosine levels activate the A2a receptor,which would reduce cytokines responsible for chronic inflammation.展开更多
AIM:To study usefulness of high-potency sucralfate(HPS)in a patient with chemoradiation mucositis and discuss its mechanism of action.METHODS:HPS,a non-covalently cross-link of sucralfate,cations and bidentate anionic...AIM:To study usefulness of high-potency sucralfate(HPS)in a patient with chemoradiation mucositis and discuss its mechanism of action.METHODS:HPS,a non-covalently cross-link of sucralfate,cations and bidentate anionic chelators,has a maintains a surface concentration of sucralfate 3 h following administration that is 7-23 fold that possible with standard-potency sucralfate.The accelerated mucosal healing and pain alleviation of HPS in patients with erosive esophageal reflux,prompted its use in this patient with chemoradiation mucositis of the oropharynx and alimentary tract.A literature-based review of the immuno-modulatory effects of sucralfate is discussed.RESULTS:Within 48 h of intervention:(1)there was complete disappearance of oral mucositis lesions;tenderness with(2)patient-reported disappearance of pain,nausea and diarrhea;patient required(3)no opiate analgesia and(4)no tube-feeding supplements to regular diet.Dysgeusia and xerostomia persisted.A modified Naranjo Questionnaire score of 10 supported the likelihood that HPS intervention caused the observed clinical effects.No adverse reactions noted.CONCLUSION:In this patient HPS was useful to treat chemo-radiation mucositis of the oropharynx and alimentary tract.HPS may directly or indirectly facilitate an immunomodulatory mechanism involving accelerated growth factor activation,which may be a new target for therapeutic intervention in such patients.展开更多
Biomaterials can modulate the local immune and repair-supportive microenvironments to promote peripheral nerve regeneration. Inorganic bioceramics have been widely used for regulating tissue regeneration and local imm...Biomaterials can modulate the local immune and repair-supportive microenvironments to promote peripheral nerve regeneration. Inorganic bioceramics have been widely used for regulating tissue regeneration and local immune response. However, little is known on whether inorganic bioceramics can have potential for enhancing peripheral nerve regeneration and what are the mechanisms underlying their actions. Here, the inorganic lithium-magnesium-silicon (Li-Mg-Si, LMS) bioceramics containing scaffolds are fabricated and characterized. The LMS-containing scaffolds had no cytotoxicity against rat Schwann cells (SCs), but promoted their migration and differentiation towards a remyelination state by up-regulating the expression of neurotrophic factors in a β-catenin-dependent manner. Furthermore, using single cell-sequencing, we showed that LMS-containing scaffolds promoted macrophage polarization towards the pro-regenerative M2-like cells, which subsequently facilitated the migration and differentiation of SCs. Moreover, implantation with the LMS-containing nerve guidance conduits (NGCs) increased the frequency of M2-like macrophage infiltration and enhanced nerve regeneration and motor functional recovery in a rat model of sciatic nerve injury. Collectively, these findings indicated that the inorganic LMS bioceramics offered a potential strategy for enhancing peripheral nerve regeneration by modulating the immune microenvironment and promoting SCs remyelination.展开更多
As probiotics in the gut, Lactobacilli are believed to play important roles in the development and maintenance of both the mucosal and systemic immune system of the host. This study was aimed to investigate the immuno...As probiotics in the gut, Lactobacilli are believed to play important roles in the development and maintenance of both the mucosal and systemic immune system of the host. This study was aimed to investigate the immunomodulatory function of candiate lactobacilli on T cells. Lactobacilli were isolated from healthy human feces and the microbiological characteristics were identified by API 50 CHL and randomly amplified polymorphic DNA （RAPD） assays. Anti-CD3 antibody activated peripheral blood mononuclear cells （PBMCs） were treated by viable, heat-killed lactobacilli and genomic DNA of lactobacilli, and cytokine profiles were tested by ELISA. Isolated lactobacilli C44 and C48 were identified as L. acidophilus and L. paracacei, which have properties of acid and bile tolerance and inhibitor effects on pathogens. Viable and heat-killed C44 and C48 induced low levels of proinflammatory cytokines （TNF-a, IL-6 and IL-8） and high levels of IFN-y and IL-12p70 in PBMCs. In anti- CD3 antibody activated PBMCs, viable and heat-killed C44 increased Th2 cytokine levels （IL-5, IL-6 and IL-10）, and simultaneously enhanced Thl responses by inducing IFN-y and IL-12p70 production. Different from that of lactabacillus strains, their genomic DNA induced low levels of IL-12p70, IFN-y and proinflammatory cytokines in PBMCs with or without anti-CD3 antibody activation. These results provided in vitro evidence that the genomic DNA of strains of C44 and C48, especially C44, induced weaker inflammation, and may be potentially applied for treating allergic diseases.展开更多
The paracrine and immunomodulatory cytokines secreted by mesenchymal stem cells(MSCs),generally referred to as the MSCs derived secretome,has substantial potential for the treatment of many chronic and degenerative di...The paracrine and immunomodulatory cytokines secreted by mesenchymal stem cells(MSCs),generally referred to as the MSCs derived secretome,has substantial potential for the treatment of many chronic and degenerative diseases.MSCs secretome contains both common and disease specific cytokines and modulators that can be beneficial against a wide range of chronic diseases.Herein,we discuss the MSCs secretome composition profile and its translational applicability and the challenges surrounding its use in clinical settings.展开更多
Cancer induces tolerance by suppressing immune function, modulating the T helper activity and causing an imbalance of cytokines produced by T cells. IL-12 is an immune regulatory cytokine with potent anti-tumor activi...Cancer induces tolerance by suppressing immune function, modulating the T helper activity and causing an imbalance of cytokines produced by T cells. IL-12 is an immune regulatory cytokine with potent anti-tumor activity and its signalling network leads to polarization of na?ve CD4+ T cells into Th1. In pre-clinical studies, administration of recombinant IL-12 by intravenous injection or IL-12 plasmid DNA by intra-tumoral injection showed some anti-tumor effects, measurable immunological responses, but also important dose-dependent side effects. We investigated the ability of low doses of IL-12 to modulate the T cell subpopulations in cultures of PBMCs derived from Non Small Lung Cancer (NSCLC) patients and to induce lysis of lung adenocarcinoma cells by T cells. PBMCs were stimulated with different doses of IL-12 and T cell phenotype was evaluated. IL-12 at 0.01 pg/ml significantly increased the number of CD4 and CD8 T cells, in particular of CD4/IFNγ producing cells. IL-12 did not stimulate T regulatory, but it increased the lysis of lung adenocarcinoma cells induced by T cells. Our results showed that low doses of IL-12 modulates T cell sub-populations in vitro and it increased their lytic activity on adenocarcinoma cells, thus we hypothesize the use of low dose of IL-12 as a therapeutic tool against pathologies characterized by a T cell imbalance, in order to promote an immuno-modulation.展开更多
CD8 is a cell surface glycoprotein found in cytotoxic T lymphocytes,which are important components in cellular immunity,esp.in the immune response to cancer and chronic infections.There are two forms of CD8, either as...CD8 is a cell surface glycoprotein found in cytotoxic T lymphocytes,which are important components in cellular immunity,esp.in the immune response to cancer and chronic infections.There are two forms of CD8, either as an αα homodimer or αβ heterodimer.It acts as an“assistant”or co-receptor in the function of cytotoxic T cells where specific immunity is mediated by interaction of specific T cell receptor(αβTCR)and its ligand peptide major histocompatibility complex(pMHC).CD8 also binds to pMHC but away from the interface of pMHC and TCR contact,thereof no influence on the specificity of this interaction.If the TCR and CD8 bind to the same pMHC at the same time,CD8 is defined as a co-receptor,functioning through its signalling via its cytoplasmic tyrosine phosphorylation pathway;if CD8 binds to pMHC independently of the TCR,it is defined as an adhesion molecule.At present,the co-receptor function theory is dominated in the field. Recent study has also shown that murine CD8αα binds to TL antigen,an MHC homologue,therefore acts as an immuno-modulator.In this review,we discuss these current understandings of the three aspects of the CD8 functions and their structural basis.Cellular & Molecular Immunology.2004;1(2):81-88.展开更多
文摘In order to analyze the mechanism of immunomodulation by LPS on murine peritoneal suppressor macrophages, we have, using RNase protection assay,checked the changes of mRNA expression pattern of several cytokine genes during the immuno-modulation.It has been found that, after treating peritoneal suppressor macrophages with LPS, mRNAs of IL-12 p35, IL-12 p40,IL-6 and IFN-γ are newly appeared, while those of IL-1α, IL-1β and IL-1Ra are increased and those of other cytokines, like TGF-β1 and MIF are not changed at all.It seems certain that those cytokines, whose expression is increased by LPS stimulation, may be responsible for the functional changes of suppressor macrophages during immuno-modulation. Among these changes, the appearance of IL-12 mRNA may play a critical role, and, in this regard, the synergetic effect between IFN-γ and LPS on the increase of IL-12 p35 and IL-12 p40 mRNA expression is an interesting finding.
基金supported by Science and Technology Project of Jiangxi Province(2009BSB10909)
文摘Objective To investigate the effects of estrogen(E_2)level on regulatory T cells(Treg)in peripheral blood during pregnancy.Methods:A total of 30 healthy non-pregnant women were selected as control group,90 pregnant women of early,middle and late pregnancy and 30 postpartum women at 1 month after parturition were selected as experimental groups including early pregnancy group,middle pregnancy group and late pregnancy group;the proportions of CD4^+CD25^+Treg and CD4^+CD25^+CD127^-Treg among CD4 T cells were detected by flow cytometry;the serum estrogen content in peripheral blood was detected by electrochemical immune luminescence method.Results:E_2 level was coincident with the change of Tregs number during pregnancy.The estrogen content in peripheral blood increased gradually from early pregnancy to late pregnancy,then decreased significantly after parturition,and the level at 1 month after parturition down to the level in non-pregnancy group(P>0.05);the level of E_2 in pregnancy groups were significantly higher than those in non-pregnancy group(P<0.01);and there were significant differences among early pregnancy group,middle pregnancy group and late pregnancy group(P<0.05).The proportions of CD4^+CD25^+Treg and CD4^+CD25^+CD127^-Treg in pregnancy groups were significantly higher than those in non-pregnancy group(P<0.05),but decreased significantly after parturition,and there was no significant difference between non-pregnancy group and postpartum women group(P>0.05):the proportions in middle and late pregnancy groups were significantly higher than those in early pregnancy group(P<0.05).but decreased slightly in late pregnancy group,there was no significant difference between late pregnancy group and middle pregnancy group(P>0.05).There was correlation between Tregs number with estrogen level during pregnancy.The proportion of CD4^+CD25^+Treg and CD4^+CD25^+CD 127^-Treg were positively correlated with estrogen level.Conclusions:High proportion of CD4^+CD25^+Trcg and CD4^+CD25^+CD127^-Treg is closely related to the high level of E,during pregnancy.It suggested that high level of estrogen may induce an increase of CD4^+CD25^+Treg in peripheral blood.and then influence the immune function of pregnant women.The results of this experiment might play an important role of estrogen in immune-modulation during pregnancy.
基金Supported by A research grant(DK-018777)from the National Institute of Diabetes and Digestive and Kidney Diseases
文摘Inflammatory bowel disease(IBD)is a common and lifelong disabling gastrointestinal disease.Emerging treatments are being developed to target inflammatory cytokines which initiate and perpetuate the immune response.Adenosine is an important modulator of inflammation and its anti-inflammatory effects have been well established in humans as well as in animal models.High extracellular adenosine suppresses and resolves chronic inflammation in IBD models.High extracellular adenosine levels could be achieved by enhanced adenosine absorption and increased de novo synthesis.Increased adenosine concentration leads to activation of the A2a receptor on the cell surface of immune and epithelial cells that would be a potential therapeutic target for chronic intestinal inflammation. Adenosine is transported via concentrative nucleoside transporter and equilibrative nucleoside transporter transporters that are localized in apical and basolateral membranes of intestinal epithelial cells,respectively. Increased extracellular adenosine levels activate the A2a receptor,which would reduce cytokines responsible for chronic inflammation.
基金Supported by Translation Medicine Research Compassionate Use Program of MMI,No.2006-001Data collection was funded as part of Mueller Medical International LLC research on polyanionic saccharides as in-vivo surface active immuno-modulating agents for epithelial mediated processes at its Center for Translational Medicine Research in Foster Rhode Island
文摘AIM:To study usefulness of high-potency sucralfate(HPS)in a patient with chemoradiation mucositis and discuss its mechanism of action.METHODS:HPS,a non-covalently cross-link of sucralfate,cations and bidentate anionic chelators,has a maintains a surface concentration of sucralfate 3 h following administration that is 7-23 fold that possible with standard-potency sucralfate.The accelerated mucosal healing and pain alleviation of HPS in patients with erosive esophageal reflux,prompted its use in this patient with chemoradiation mucositis of the oropharynx and alimentary tract.A literature-based review of the immuno-modulatory effects of sucralfate is discussed.RESULTS:Within 48 h of intervention:(1)there was complete disappearance of oral mucositis lesions;tenderness with(2)patient-reported disappearance of pain,nausea and diarrhea;patient required(3)no opiate analgesia and(4)no tube-feeding supplements to regular diet.Dysgeusia and xerostomia persisted.A modified Naranjo Questionnaire score of 10 supported the likelihood that HPS intervention caused the observed clinical effects.No adverse reactions noted.CONCLUSION:In this patient HPS was useful to treat chemo-radiation mucositis of the oropharynx and alimentary tract.HPS may directly or indirectly facilitate an immunomodulatory mechanism involving accelerated growth factor activation,which may be a new target for therapeutic intervention in such patients.
基金supported by a grant from the National Natural Science Foundation of China(81900968)Shanghai Sailing Program(20YF1409900)Shanghai Anticancer Association EYAS PROJECT(SACA-CY21A01 and SACA-CY22A01).
文摘Biomaterials can modulate the local immune and repair-supportive microenvironments to promote peripheral nerve regeneration. Inorganic bioceramics have been widely used for regulating tissue regeneration and local immune response. However, little is known on whether inorganic bioceramics can have potential for enhancing peripheral nerve regeneration and what are the mechanisms underlying their actions. Here, the inorganic lithium-magnesium-silicon (Li-Mg-Si, LMS) bioceramics containing scaffolds are fabricated and characterized. The LMS-containing scaffolds had no cytotoxicity against rat Schwann cells (SCs), but promoted their migration and differentiation towards a remyelination state by up-regulating the expression of neurotrophic factors in a β-catenin-dependent manner. Furthermore, using single cell-sequencing, we showed that LMS-containing scaffolds promoted macrophage polarization towards the pro-regenerative M2-like cells, which subsequently facilitated the migration and differentiation of SCs. Moreover, implantation with the LMS-containing nerve guidance conduits (NGCs) increased the frequency of M2-like macrophage infiltration and enhanced nerve regeneration and motor functional recovery in a rat model of sciatic nerve injury. Collectively, these findings indicated that the inorganic LMS bioceramics offered a potential strategy for enhancing peripheral nerve regeneration by modulating the immune microenvironment and promoting SCs remyelination.
基金supported by Global Watch International Secondment ChinaUK Department of Trade and Industry
文摘As probiotics in the gut, Lactobacilli are believed to play important roles in the development and maintenance of both the mucosal and systemic immune system of the host. This study was aimed to investigate the immunomodulatory function of candiate lactobacilli on T cells. Lactobacilli were isolated from healthy human feces and the microbiological characteristics were identified by API 50 CHL and randomly amplified polymorphic DNA （RAPD） assays. Anti-CD3 antibody activated peripheral blood mononuclear cells （PBMCs） were treated by viable, heat-killed lactobacilli and genomic DNA of lactobacilli, and cytokine profiles were tested by ELISA. Isolated lactobacilli C44 and C48 were identified as L. acidophilus and L. paracacei, which have properties of acid and bile tolerance and inhibitor effects on pathogens. Viable and heat-killed C44 and C48 induced low levels of proinflammatory cytokines （TNF-a, IL-6 and IL-8） and high levels of IFN-y and IL-12p70 in PBMCs. In anti- CD3 antibody activated PBMCs, viable and heat-killed C44 increased Th2 cytokine levels （IL-5, IL-6 and IL-10）, and simultaneously enhanced Thl responses by inducing IFN-y and IL-12p70 production. Different from that of lactabacillus strains, their genomic DNA induced low levels of IL-12p70, IFN-y and proinflammatory cytokines in PBMCs with or without anti-CD3 antibody activation. These results provided in vitro evidence that the genomic DNA of strains of C44 and C48, especially C44, induced weaker inflammation, and may be potentially applied for treating allergic diseases.
文摘The paracrine and immunomodulatory cytokines secreted by mesenchymal stem cells(MSCs),generally referred to as the MSCs derived secretome,has substantial potential for the treatment of many chronic and degenerative diseases.MSCs secretome contains both common and disease specific cytokines and modulators that can be beneficial against a wide range of chronic diseases.Herein,we discuss the MSCs secretome composition profile and its translational applicability and the challenges surrounding its use in clinical settings.
文摘Cancer induces tolerance by suppressing immune function, modulating the T helper activity and causing an imbalance of cytokines produced by T cells. IL-12 is an immune regulatory cytokine with potent anti-tumor activity and its signalling network leads to polarization of na?ve CD4+ T cells into Th1. In pre-clinical studies, administration of recombinant IL-12 by intravenous injection or IL-12 plasmid DNA by intra-tumoral injection showed some anti-tumor effects, measurable immunological responses, but also important dose-dependent side effects. We investigated the ability of low doses of IL-12 to modulate the T cell subpopulations in cultures of PBMCs derived from Non Small Lung Cancer (NSCLC) patients and to induce lysis of lung adenocarcinoma cells by T cells. PBMCs were stimulated with different doses of IL-12 and T cell phenotype was evaluated. IL-12 at 0.01 pg/ml significantly increased the number of CD4 and CD8 T cells, in particular of CD4/IFNγ producing cells. IL-12 did not stimulate T regulatory, but it increased the lysis of lung adenocarcinoma cells induced by T cells. Our results showed that low doses of IL-12 modulates T cell sub-populations in vitro and it increased their lytic activity on adenocarcinoma cells, thus we hypothesize the use of low dose of IL-12 as a therapeutic tool against pathologies characterized by a T cell imbalance, in order to promote an immuno-modulation.
文摘CD8 is a cell surface glycoprotein found in cytotoxic T lymphocytes,which are important components in cellular immunity,esp.in the immune response to cancer and chronic infections.There are two forms of CD8, either as an αα homodimer or αβ heterodimer.It acts as an“assistant”or co-receptor in the function of cytotoxic T cells where specific immunity is mediated by interaction of specific T cell receptor(αβTCR)and its ligand peptide major histocompatibility complex(pMHC).CD8 also binds to pMHC but away from the interface of pMHC and TCR contact,thereof no influence on the specificity of this interaction.If the TCR and CD8 bind to the same pMHC at the same time,CD8 is defined as a co-receptor,functioning through its signalling via its cytoplasmic tyrosine phosphorylation pathway;if CD8 binds to pMHC independently of the TCR,it is defined as an adhesion molecule.At present,the co-receptor function theory is dominated in the field. Recent study has also shown that murine CD8αα binds to TL antigen,an MHC homologue,therefore acts as an immuno-modulator.In this review,we discuss these current understandings of the three aspects of the CD8 functions and their structural basis.Cellular & Molecular Immunology.2004;1(2):81-88.
