Patients with steroid-resistant asthma had their monocyte-derived TH17 cells collected. The expression levels of ERK2 in the TH17 were silenced and inhibited using ERK2 specific small interfering RNA (siRNA). By scree...Patients with steroid-resistant asthma had their monocyte-derived TH17 cells collected. The expression levels of ERK2 in the TH17 were silenced and inhibited using ERK2 specific small interfering RNA (siRNA). By screening of CXCL1 and IL-17A in the TH17 culture supernatant, the expression levels of ERK2 and CXCL1 were determined. Using targeted siRNA to inhibit ERK2, the expression of ERK2 in the TH17 was reduced. Furthermore, inhibiting ERK2 hindered CXCL1 expression and decreased CXCL1 and IL-17A production. These findings suggest that ERK2 is involved in the synthesis of CXCL1 and IL-17A, two proteins that play a key role in the pathogenesis of hormone-resistant asthma.展开更多
HTLV-1(human T-lymphotropic virus type 1)causes chronic infection ofhuman T lymphocytes.HTLV-1 infection is known to be related to multiple diseases,including neoplastic growth of HTLV-1-infected T cells(ATL)and neopl...HTLV-1(human T-lymphotropic virus type 1)causes chronic infection ofhuman T lymphocytes.HTLV-1 infection is known to be related to multiple diseases,including neoplastic growth of HTLV-1-infected T cells(ATL)and neoplastic inflammatory conditions,such as HTLV-1-associated myelopathy/tropical spastic paraparesis(HAM/TSP),Sjogren's syndrome with arthritis,polymyositis uveitis,and bronchoalveolitis.Regulatory T cells(Tregs)regulate inflammatory cells,such as Th17 cells.The purpose of this study was to evaluate Tregs and Th17 cells,as well as the expression of related transcription factors(ROR-γ1 and FOXP3)and cytokines(IL-10,TGF-β,IL-6,and IL-17A)in HTLV-1 infection.展开更多
The etiopathology of inflammatory bowel disease(IBD)remains elusive.Accumulating evidence suggests that the abnormality of innate and adaptive immunity responses plays an important role in intestinal inflammation.IBD ...The etiopathology of inflammatory bowel disease(IBD)remains elusive.Accumulating evidence suggests that the abnormality of innate and adaptive immunity responses plays an important role in intestinal inflammation.IBD including Crohn's disease(CD)and ulcerative colitis(UC)is a chronic inflammatory disease of the gastrointestinal tract,which is implicated in an inappropriate and overactive mucosal immune response to luminalflora.Traditionally,CD is regarded as a Th1-mediated inflammatory disorder while UC is regarded as a Th2-like disease.Recently,Th17 cells were identif ied as a new subset of T helper cells unrelated to Th1 or Th2 cells,and several cytokines [e.g.interleukin(IL)-21,IL-23] are involved in regulating their activation and differentiation.They not only play an important role in host defense against extracellular pathogens,but are also associated with the development of autoimmunity and inflammatory response such as IBD.The identif ication of Th17 cells helps us to explain some of the anomalies seen in the Th1/Th2 axis and has broadened our understanding of the immunopathological effects of Th17 cells in the development of IBD.展开更多
AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into ...AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into the study, 50 patients with HBV-related ACLF and 29 patients with chronic hepatitis B (CHB), from the First Affiliated Hospital of Medical College from January 2009 to June 2012. The ACLF patients were diagnosed according to the criteria recommended by The 19th Conference of the Asian Pacific Association for the Study of the Liver in 2009. Twenty healthy individuals with a similar gender and age structures to the two patient groups were also included as the normal controls (NC). Of the 50 ACLF patients, 28 were subsequently classified as non-survivors: 19 patients died from multiorgan failure, 3 underwent liver transplantation, and 6 discontinued therapy during follow-up because of financial reasons. The remaining 22 ACLF patients whose liver and anticoagulation function recovered to nearly normal levels within the next 6 mo were classified as survivors. The number of circulating Treg and Th17 cells was determined upon diagnosis and during the 8th week of follow-up through flow cytometry. RESULTS: The percentage of circulating Treg cells in the ACLF group was significantly higher than that in the CHB group (5.50% ± 1.15% vs 3.30% ± 1.13%, P < 0.01). The percentages of circulating Th17 cells in the ACLF and the CHB groups were significantly higher than that in the NC group (6.32% ± 2.22% vs 1.56% ± 0.44%, P < 0.01; 3.53% ± 1.65% vs 1.56% ± 0.44%, P < 0.01). No significant difference in Treg cell to Th17 cell ratio was observed between the ACLF group and the CHB group (0.98 ± 0.44 vs 1.12 ± 0.64, P = 0.991), whereas those in the two HBV infection groups were significantly lower than that in the NC group (1.85 ± 1.22; both P < 0.01). The percentage of Treg cells in the survivors during the 8th week of follow-up was significantly lower than that during peak ACLF severity [total bilirubin (TBIL) peak] (3.45% ± 0.97% vs 5.18% ± 1.02%, P < 0.01). The percentage of Th17 cells in survivors during the 8th week of follow-up was significantly lower than that during the peak TBIL (2.89% ±0.60% vs 5.24% ± 1.46%; P < 0.01). The Treg cell to Th17 cell ratio during the 8 th week of follow-up was significantly higher than that during the TBIL peak (1.22 ± 0.36 vs 1.10 ± 0.54; P < 0.05). CONCLUSION: Restoring the Treg cell to Th17 cell ratio during the follow-up phase of ACLF could maintain the immune system at a steady state, which favours good prognosis.展开更多
AIM: To explore the preventive and therapeutic effects of Faecalibacterium prausnitzii(F. prausnitzii) supernatant on dextran sulfate sodium(DSS) induced colitis in mice.METHODS: Forty C57BL/6J male mice were randomly...AIM: To explore the preventive and therapeutic effects of Faecalibacterium prausnitzii(F. prausnitzii) supernatant on dextran sulfate sodium(DSS) induced colitis in mice.METHODS: Forty C57BL/6J male mice were randomlydivided into four groups: control group, model group, treatment group, and prevention group. Mice were weighed daily. On day 10, the colon length was measured, the colorectal histopathologic damage score(HDS) was assessed, and plasma interleukin(IL)-17 A, IL-6, and IL-4 levels were detected by enzyme-linked immunosorbent assay. The expression of transcription factor retinoic acid-related orphan receptor-γt(RORγt) and IL-17 A in colon inflammatory mucosa tissue were determined by immunohistochemical assay, and the expression levels of RORγt m RNA, IL-17 A m RNA, and IL-6 m RNA were detected by real-time quantitative polymerase chain reaction(PCR). The proportion of Th17 in mononuclear cells in spleen was assayed by fluorescence activated cell sorter. RESULTS: When compared with the model group, the colon length(P < 0.05) and body weight(P < 0.01) in the treatment and prevention groups were significantly increased, and the colon HDS was decreased(P < 0.05 and P < 0.01). There was no statistical difference between the treatment group and prevention group. After treatment with F. prausnitzii supernatant, the plasma levels of IL-17 A and IL-6(P < 0.05), the protein and m RNA expression of IL-17 A and RORγt, and the Th17 cell ratio of spleen cells(P < 0.01) were significantly decreased compared to the model group. Plasma IL-4 level in the prevention group was significantly higher than that in the model group(P < 0.05), but there was no significant difference between these two groups in the expression of IL-6 in both the plasma and colon mucosa tissues.CONCLUSION: F. prausnitzii supernatant exerts protective and therapeutic effects on DSS-induced colitis in mice, probably via inhibition of Th17 differentiation and IL- 17A secretion in the plasma and colon mucosa tissues. It can also improve colitis in mice by downregulating IL-6 and prevent colitis by upregulating IL-4.展开更多
AIM: To perform a comprehensive investigation into the potential correlation between circulating myeloidderived suppressor cells (MDSCs) and Th17 cells in esophageal cancer (ECA). METHODS: A total of 31 patients newly...AIM: To perform a comprehensive investigation into the potential correlation between circulating myeloidderived suppressor cells (MDSCs) and Th17 cells in esophageal cancer (ECA). METHODS: A total of 31 patients newly diagnosed with ECA and 26 healthy subjects were included in the current study. The frequencies of MDSCs and Th17 cells in peripheral blood were determined by flow cytometry. The mRNA expression of cytokines, arginase 1 (Arg1) and inducible NO synthase (iNOS) in peripheral blood mononuclear cells (PBMCs) and plasma Arg1 were assessed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: There was an increased prevalence of MDSCs in the peripheral blood from ECA patients (15.21% ± 2.25%) when compared with healthy control (HC) (1.10% ± 0.12%, P < 0.0001). The plasma levels of Arg1 in ECA patients were significantly higher than those in HC (28.28 ± 4.10 ng/mL vs 9.57 ± 1.51 ng/ mL, P=0.0003). iNOS mRNA levels in the peripheral blood of ECA patients also showed a threefold increase compared with HC (P=0.0162). The frequencies of Th17 cells (CD4 + IL-17A + ) were significantly elevated in ECA patients versus HC (3.50% ± 0.33% vs 1.82% ± 0.19%, P=0.0001). Increased mRNA expression of IL-17 and ROR-γt was also observed in ECA patients compared with HC (P=0.0041 and P=0.0004, respectively), while the mRNA expression of IL-6 and tumor necrosis factor-α (TNF-α) showed significant decreases (P=0.0049 and P < 0.0001, respectively). No obvious correlations were found between the frequencies of MDSCs and Th17 cells in the peripheral blood from ECA patients(r=-0.1725, P=0.3534). Arg1 mRNA levels were positively correlated with levels of IL-6 (r=0.6404, P=0.0031) and TNF-α (r=0.7646, P=0.0001). Similarly, iNOS mRNA levels were also positively correlated with levels of IL-6 (r=0.6782, P=0.0007) and TNF-α (r=0.7633, P < 0.0001). CONCLUSION: This study reveals the relationship between circulating MDSCs and Th17 cells, which may lead to new immunotherapy approaches for ECA based on the associated metabolites and cytokines.展开更多
· AIM: To determine the effects of rapamycin on experimental autoimmune uveoretinitis(EAU) and investigate of role of rapamycin on T cell subsets in the disease.·METHODS: EAU was induced in rats using peptid...· AIM: To determine the effects of rapamycin on experimental autoimmune uveoretinitis(EAU) and investigate of role of rapamycin on T cell subsets in the disease.·METHODS: EAU was induced in rats using peptides1169 to 1191 of the interphotoreceptor binding protein(IRBP). Rapamycin(0.2 mg/kg/d) was administrated by intraperitoneal injection for a consecutive 7d after immunization. Th1/Th2/Th17 cytokines, TGF-β1, and IL-6produced by lymphocyteswere measured by ELISA, while Th17 cells and CD4 +CD25 + regulatory T cells(Tregs)from rat spleen were detected by flow cytometry.·RESULTS: Intraperitoneal treatment immediately after immunization dramatically ameliorated the clinical course of EAU. Clinical responses were associated with reduced retinal inflammatory cell infiltration and tissue destruction. Rapamycin induced suppression of Th1/Th2/Th17 cytokines, including IFN-γ, IL-2, IL-17, IL-4, and IL-10 release from T lymphocytes of EAU rats, in vitro.Rapamycin also significantly increased TGF-β1production but had no effect on IL-6 productionof T lymphocytes from EAU rats in vitro. Furthermore,rapamycin decreased the ratio of Th17 cells/CD4 +T cells and upregulated Tregs in EAU, as detected by flow cytometry.·CONCLUSION: Rapamycin effectively interferes with T cell mediated autoimmune uveitis by inhibiting antigen-specific T cell functions and enhancing Tregs in EAU.Rapamycin is a promising new alternative as an adjunct corticosteroid-sparing agent for treating uveitis.展开更多
AIM To investigate T-cell activation, the percentage of peripheral T regulatory cells(Tregs), Th17 cells and the circulating cytokine profile in systemic sclerosis(SSc).METHODS We enrolled a total of 24 SSc patients a...AIM To investigate T-cell activation, the percentage of peripheral T regulatory cells(Tregs), Th17 cells and the circulating cytokine profile in systemic sclerosis(SSc).METHODS We enrolled a total of 24 SSc patients and 16 healthy controls in the study and divided the patients as having diffuse cutaneous SSc(dc SSc, n = 13) or limited cutaneous SSc(lc SSc, n = 11). We performed a further subdivision of the patients regarding the stage of the disease-early, intermediate or late. Peripheral venous blood samples were collected from all subjects. We performed flow cytometric analysis of the activationcapacity of T-lymphocytes upon stimulation with PHA-M and of the percentage of peripheral Tregs and Th17 cells in both patients and healthy controls. We used ELISA to quantitate serum levels of human interleukin(IL)-6, IL-10, tissue growth factor-β1(TGF-β1), and IL-17 A.RESULTS We identified a decreased percentage of CD3+CD69+ cells in PHA-stimulated samples from SSc patients in comparison with healthy controls(13.35% ± 2.90% vs 37.03% ± 2.33%, P < 0.001). However, we did not establish a correlation between the down-regulated CD3+CD69+ cells and the clinical subset, nor regarding the stage of the disease. The activated CD4+CD25+ peripheral lymphocytes were represented in decreased percentage in patients when compared to controls(6.30% ± 0.68% vs 9.36% ± 1.08%, P = 0.016). Regarding the forms of the disease, dc SSc patients demonstrated lower frequency of CD4+CD25+ T cells against healthy subjects(5.95% ± 0.89% vs 9.36% ± 1.08%, P = 0.025). With regard to Th17 cells, our patients demonstrated increased percentage in comparison with controls(18.13% ± 1.55% vs 13.73% ± 1.21%, P = 0.031). We detected up-regulated Th17 cells within the lc SSc subset against controls(20.46% ± 2.41% vs 13.73% ± 1.21%, P = 0.025), nevertheless no difference was found between dc SSc and lc SSc patients. Flow cytometric analysis revealed an increased percentage of CD4+CD25-Foxp3+ in dc SSc patients compared to controls(10.94% ± 1.65% vs 6.88% ± 0.91, P = 0.032). Regarding the peripheral cytokine profile, we detected raised levels of IL-6 [2.10(1.05-4.60) pg/m L vs 0.00 pg/m L, P < 0.001], TGF-β1(19.94 ± 3.35 ng/m L vs 10.03 ± 2.25 ng/m L, P = 0.02), IL-10(2.83 ± 0.44 pg/m L vs 0.68 ± 0.51 pg/m L, P = 0.008), and IL-17 A [6.30(2.50-15.60) pg/m L vs 0(0.00-0.05) pg/m L, P < 0.001] in patients when compared to healthy controls. Furthermore, we found increased circulating IL-10, TGF-β, IL-6 and IL-17 A in the lc SSc subset vs control subjects, as it follows: IL-10(3.32 ± 0.59 pg/m L vs 0.68 ± 0.51 pg/m L, P = 0.003), TGF-β1(22.82 ± 4.99 ng/m L vs 10.03 ± 2.25 ng/m L, P = 0.031), IL-6 [2.08(1.51-4.69) pg/m L vs 0.00 pg/m L, P < 0.001], and IL-17 A [14.50(8.55-41.65) pg/m L vs 0.00(0.00-0.05) pg/m L, P < 0.001]. Furthermore, circulating IL-17 A was higher in lc SSc as opposed to dc SSc subset(31.99 ± 13.29 pg/m L vs 7.14 ± 3.01 pg/m L, P = 0.008). Within the dc SSc subset, raised levels of IL-17 A and IL-6 were detected vs healthy controls: IL-17 A [2.60(0.45-9.80) pg/m L vs 0.00(0.00-0.05) pg/m L, P < 0.001], IL-6 [2.80(1.03-7.23) pg/m L vs 0.00 pg/m L, P < 0.001]. Regarding the stages of the disease, TGF-β1 serum levels were increased in early stage against late stage, independently from the SSc phenotype(30.03 ± 4.59 ng/m L vs 13.08 ± 4.50 ng/m L, P = 0.017).CONCLUSION It is likely that the altered percentage of Th17 and CD4+CD25-Fox P3+ cells along with the peripheral cytokine profile in patients with SSc may play a key role in the pathogenesis of the disease.展开更多
Objective To explore whether age,disease severity,cytokines and lymphocytes in H1N1 influenza A patients correlate with viral load and clearance.Methods Total of 70 mild and 16 severe patients infected with H1N1 influ...Objective To explore whether age,disease severity,cytokines and lymphocytes in H1N1 influenza A patients correlate with viral load and clearance.Methods Total of 70 mild and 16 severe patients infected with H1N1 influenza A virus were enrolled in this study.Results It was found that the patients under 14 years old and severe patients displayed significantly higher viral loads and prolonged viral shedding periods compared with the patients over 14 years old and mild patients,respectively(P < 0.05).Moreover,the patients under 14 years old and severe patients displayed significantly lower Th17 cell frequency than the patients over 14 years old and mild patients(P < 0.01).The viral shedding period inversely correlated with the frequency of IL-17+IFN-γ-CD4+ T cells.Additionally,the decreased concentration of serum TGF-β correlated with the decreased frequency of IL-17+IFN-γ-CD4+ T cells.Conclusions Both younger and severe patients are associated with higher viral loads and longer viral shedding periods,which may partially be attributed to the impaired Th17 cell response.展开更多
Objective: To explore the expression of IL-27, Th17 cells and CD4+CD25+ regulatory T cells (Treg) as well as its associated cytokines in peripheral blood of patients with allergic rhinitis (AR). Method: From March 201...Objective: To explore the expression of IL-27, Th17 cells and CD4+CD25+ regulatory T cells (Treg) as well as its associated cytokines in peripheral blood of patients with allergic rhinitis (AR). Method: From March 2012 to May, the peripheral blood of 24 cases of AR patients (AR group) and 16 cases of healthy volunteers (control group) was collected, and the percentage of Th17 cells and Treg cells in the peripheral blood was detected by flow cytometry (FCM);the levels of IL-27, IL-17 and IL-10 in serum was detected by ELISA. Result: The percentage of Th17 cells in AR group and the control group was 1.76% ± 0.60% and 0.59% ± 0.17%, respectively. It was higher in AR group than in control group, and the difference between two groups was statistically significant (P 0.05). Conclusion: In the peripheral blood of AR patients there was a reduction of IL-27 level and imbalance of Th17/Treg cell function. IL-27 on Th17/Treg cells adjustment may play an important role on the pathogenesis of the AR.展开更多
Balanced immunity is pivotal for health and homeostasis.CD4+helper T(Th)cells are central to the balance between immune tolerance and immune rejection.Th cells adopt distinct functions to maintain tolerance and clear ...Balanced immunity is pivotal for health and homeostasis.CD4+helper T(Th)cells are central to the balance between immune tolerance and immune rejection.Th cells adopt distinct functions to maintain tolerance and clear pathogens.Dysregulation of Th cell function often leads to maladies,including autoimmunity,inflammatory disease,cancer,and infection.Regulatory T(Treg)and Th17 cells are critical Th cell types involved in immune tolerance,homeostasis,pathogenicity,and pathogen clearance.It is therefore critical to understand how Treg and Th17 cells are regulated in health and disease.Cytokines are instrumental in directing Treg and Th17 cell function.The evolutionarily conserved TGF-β(transforming growth factor-β)cytokine superfamily is of particular interest because it is central to the biology of both Treg cells that are predominantly immunosuppressive and Th17 cells that can be proinflammatory,pathogenic,and immune regulatory.How TGF-βsuperfamily members and their intricate signaling pathways regulate Treg and Th17 cell function is a question that has been intensely investigated for two decades.Here,we introduce the fundamental biology of TGF-βsuperfamily signaling,Treg cells,and Th17 cells and discuss in detail how the TGF-βsuperfamily contributes to Treg and Th17 cell biology through complex yet ordered and cooperative signaling networks.展开更多
目的探讨慢性阻塞性肺疾病急性加重期(acute exacerhation of chronic obstructive pulmonary disease,AECOPD)患者治疗前后Th17/Treg免疫平衡、呼出气一氧化氮(fraction of exhaled nitric oxide,FeNO)水平变化及对预后的影响。方法选...目的探讨慢性阻塞性肺疾病急性加重期(acute exacerhation of chronic obstructive pulmonary disease,AECOPD)患者治疗前后Th17/Treg免疫平衡、呼出气一氧化氮(fraction of exhaled nitric oxide,FeNO)水平变化及对预后的影响。方法选取AECOPD患者126例,采用肺功能检测仪测定第1秒用力呼气量(forced expiratory volume in one second,FEV1)、第1秒用力呼气量占预计值百分比(FEV1%)、用力肺活量(forced vital capacity,FVC)、用力肺活量占预计值百分比(FVC%)、第1秒用力呼气量占用力肺活量的百分比(FEV1/FVC)。并使用一氧化氮测定仪检测FeNO水平,采用全身炎性反应综合征(systemic inflammaton response syndrome,SIRS)评分进行评分,采用流式细胞仪检测血清辅助性T细胞17(T help 17cells,Th17)、调节性T细胞(T Regulatory cells,Treg)水平,比较治疗前后患者肺功能指标、FeNO水平、SIRS评分、Th17/Treg水平等指标变化情况。结果治疗3个月后,AECOPD患者FEV1%、FEV1/FVC、Th17、Th17/Treg水平显著高于治疗前,FeNO、血清Treg水平、SIRS评分显著低于治疗前(P<0.05)。126例AECOPD患者治疗3个月后存活94例(74.60%);死亡32例(25.40%)。存活组FEV1%、FEV1/FVC、Treg水平显著高于死亡组,FeNO、Th17、Th17/Treg及SIRS评分显著低于死亡组(P<0.05)。多因素Logistic回归分析结果显示,治疗前FEV1%、FEV1/FVC、Treg是AECOPD患者预后的危险因素(P<0.05);FeNO、Th17、Th17/Treg、SIRS评分是AECOPD患者预后的保护因素(P<0.05)。结论AECOPD患者治疗后肺功能提高,Th17/Treg、FeNO降低,肺功能、Th17/Treg免疫平衡、FeNO水平对AECOPD患者疗效评估及预后判断具有重要意义。展开更多
Objective:To investigate the detection of Th17/Treg cell-related factors in patients with gestational diabetes mellitus(GDM)and its clinical significance.Methods:In this study,a retrospective cohort research method wa...Objective:To investigate the detection of Th17/Treg cell-related factors in patients with gestational diabetes mellitus(GDM)and its clinical significance.Methods:In this study,a retrospective cohort research method was used to collect the clinical data of 42 patients who were hospitalized in the Affiliated Hospital of Hebei University and received the diagnosis of GDM from January 2018 to December 2022,as well as 42 patients with normal pregnancies during the same period.The Th17/Treg expression levels and metabolism-related indexes in the peripheral blood of patients were detected by radioimmunoassay.Results:The relative expression of Th17 in the serum of patients in the GDM group was significantly higher than that of the control group,and the level of Treg was significantly lower than that of the control group(P<0.05);the levels of FBG,FINS,2hBG,TC,TG and HOMA-IR of the patients in the GDM group were significantly higher than that of the control group,and the level of HOMA-βwas significantly lower than that of the control group(P<0.05).Conclusion:The imbalance of the Th17/Treg cell ratio in patients with GDM may be related to their disease progression and prognosis,providing new ideas and strategies for the clinical treatment of GDM.展开更多
文摘Patients with steroid-resistant asthma had their monocyte-derived TH17 cells collected. The expression levels of ERK2 in the TH17 were silenced and inhibited using ERK2 specific small interfering RNA (siRNA). By screening of CXCL1 and IL-17A in the TH17 culture supernatant, the expression levels of ERK2 and CXCL1 were determined. Using targeted siRNA to inhibit ERK2, the expression of ERK2 in the TH17 was reduced. Furthermore, inhibiting ERK2 hindered CXCL1 expression and decreased CXCL1 and IL-17A production. These findings suggest that ERK2 is involved in the synthesis of CXCL1 and IL-17A, two proteins that play a key role in the pathogenesis of hormone-resistant asthma.
文摘HTLV-1(human T-lymphotropic virus type 1)causes chronic infection ofhuman T lymphocytes.HTLV-1 infection is known to be related to multiple diseases,including neoplastic growth of HTLV-1-infected T cells(ATL)and neoplastic inflammatory conditions,such as HTLV-1-associated myelopathy/tropical spastic paraparesis(HAM/TSP),Sjogren's syndrome with arthritis,polymyositis uveitis,and bronchoalveolitis.Regulatory T cells(Tregs)regulate inflammatory cells,such as Th17 cells.The purpose of this study was to evaluate Tregs and Th17 cells,as well as the expression of related transcription factors(ROR-γ1 and FOXP3)and cytokines(IL-10,TGF-β,IL-6,and IL-17A)in HTLV-1 infection.
基金Supported by Grants From the National Natural Science Foundation of China,No.30770988 and No.30971358
文摘The etiopathology of inflammatory bowel disease(IBD)remains elusive.Accumulating evidence suggests that the abnormality of innate and adaptive immunity responses plays an important role in intestinal inflammation.IBD including Crohn's disease(CD)and ulcerative colitis(UC)is a chronic inflammatory disease of the gastrointestinal tract,which is implicated in an inappropriate and overactive mucosal immune response to luminalflora.Traditionally,CD is regarded as a Th1-mediated inflammatory disorder while UC is regarded as a Th2-like disease.Recently,Th17 cells were identif ied as a new subset of T helper cells unrelated to Th1 or Th2 cells,and several cytokines [e.g.interleukin(IL)-21,IL-23] are involved in regulating their activation and differentiation.They not only play an important role in host defense against extracellular pathogens,but are also associated with the development of autoimmunity and inflammatory response such as IBD.The identif ication of Th17 cells helps us to explain some of the anomalies seen in the Th1/Th2 axis and has broadened our understanding of the immunopathological effects of Th17 cells in the development of IBD.
基金Supported by The Major National Science and Technology Projects for Infectious Diseases (11th and 12th Five Year, China),No. 2008ZX10002-007, No. 2012ZX10002-007the Foundation of Shaanxi Provincial Science and Technology Plan Projects,No. 2011K14-09-09
文摘AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into the study, 50 patients with HBV-related ACLF and 29 patients with chronic hepatitis B (CHB), from the First Affiliated Hospital of Medical College from January 2009 to June 2012. The ACLF patients were diagnosed according to the criteria recommended by The 19th Conference of the Asian Pacific Association for the Study of the Liver in 2009. Twenty healthy individuals with a similar gender and age structures to the two patient groups were also included as the normal controls (NC). Of the 50 ACLF patients, 28 were subsequently classified as non-survivors: 19 patients died from multiorgan failure, 3 underwent liver transplantation, and 6 discontinued therapy during follow-up because of financial reasons. The remaining 22 ACLF patients whose liver and anticoagulation function recovered to nearly normal levels within the next 6 mo were classified as survivors. The number of circulating Treg and Th17 cells was determined upon diagnosis and during the 8th week of follow-up through flow cytometry. RESULTS: The percentage of circulating Treg cells in the ACLF group was significantly higher than that in the CHB group (5.50% ± 1.15% vs 3.30% ± 1.13%, P < 0.01). The percentages of circulating Th17 cells in the ACLF and the CHB groups were significantly higher than that in the NC group (6.32% ± 2.22% vs 1.56% ± 0.44%, P < 0.01; 3.53% ± 1.65% vs 1.56% ± 0.44%, P < 0.01). No significant difference in Treg cell to Th17 cell ratio was observed between the ACLF group and the CHB group (0.98 ± 0.44 vs 1.12 ± 0.64, P = 0.991), whereas those in the two HBV infection groups were significantly lower than that in the NC group (1.85 ± 1.22; both P < 0.01). The percentage of Treg cells in the survivors during the 8th week of follow-up was significantly lower than that during peak ACLF severity [total bilirubin (TBIL) peak] (3.45% ± 0.97% vs 5.18% ± 1.02%, P < 0.01). The percentage of Th17 cells in survivors during the 8th week of follow-up was significantly lower than that during the peak TBIL (2.89% ±0.60% vs 5.24% ± 1.46%; P < 0.01). The Treg cell to Th17 cell ratio during the 8 th week of follow-up was significantly higher than that during the TBIL peak (1.22 ± 0.36 vs 1.10 ± 0.54; P < 0.05). CONCLUSION: Restoring the Treg cell to Th17 cell ratio during the follow-up phase of ACLF could maintain the immune system at a steady state, which favours good prognosis.
基金Supported by National Natural Science Foundation of China,No.81470819
文摘AIM: To explore the preventive and therapeutic effects of Faecalibacterium prausnitzii(F. prausnitzii) supernatant on dextran sulfate sodium(DSS) induced colitis in mice.METHODS: Forty C57BL/6J male mice were randomlydivided into four groups: control group, model group, treatment group, and prevention group. Mice were weighed daily. On day 10, the colon length was measured, the colorectal histopathologic damage score(HDS) was assessed, and plasma interleukin(IL)-17 A, IL-6, and IL-4 levels were detected by enzyme-linked immunosorbent assay. The expression of transcription factor retinoic acid-related orphan receptor-γt(RORγt) and IL-17 A in colon inflammatory mucosa tissue were determined by immunohistochemical assay, and the expression levels of RORγt m RNA, IL-17 A m RNA, and IL-6 m RNA were detected by real-time quantitative polymerase chain reaction(PCR). The proportion of Th17 in mononuclear cells in spleen was assayed by fluorescence activated cell sorter. RESULTS: When compared with the model group, the colon length(P < 0.05) and body weight(P < 0.01) in the treatment and prevention groups were significantly increased, and the colon HDS was decreased(P < 0.05 and P < 0.01). There was no statistical difference between the treatment group and prevention group. After treatment with F. prausnitzii supernatant, the plasma levels of IL-17 A and IL-6(P < 0.05), the protein and m RNA expression of IL-17 A and RORγt, and the Th17 cell ratio of spleen cells(P < 0.01) were significantly decreased compared to the model group. Plasma IL-4 level in the prevention group was significantly higher than that in the model group(P < 0.05), but there was no significant difference between these two groups in the expression of IL-6 in both the plasma and colon mucosa tissues.CONCLUSION: F. prausnitzii supernatant exerts protective and therapeutic effects on DSS-induced colitis in mice, probably via inhibition of Th17 differentiation and IL- 17A secretion in the plasma and colon mucosa tissues. It can also improve colitis in mice by downregulating IL-6 and prevent colitis by upregulating IL-4.
基金Supported by Grants from the Natural Science Foundation of China, No. 30872335, 81172871The Natural Science Foundation of Jiangsu Province, No. BK2009208the Jiangsu Government Scholarship for Overseas Studies
文摘AIM: To perform a comprehensive investigation into the potential correlation between circulating myeloidderived suppressor cells (MDSCs) and Th17 cells in esophageal cancer (ECA). METHODS: A total of 31 patients newly diagnosed with ECA and 26 healthy subjects were included in the current study. The frequencies of MDSCs and Th17 cells in peripheral blood were determined by flow cytometry. The mRNA expression of cytokines, arginase 1 (Arg1) and inducible NO synthase (iNOS) in peripheral blood mononuclear cells (PBMCs) and plasma Arg1 were assessed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: There was an increased prevalence of MDSCs in the peripheral blood from ECA patients (15.21% ± 2.25%) when compared with healthy control (HC) (1.10% ± 0.12%, P < 0.0001). The plasma levels of Arg1 in ECA patients were significantly higher than those in HC (28.28 ± 4.10 ng/mL vs 9.57 ± 1.51 ng/ mL, P=0.0003). iNOS mRNA levels in the peripheral blood of ECA patients also showed a threefold increase compared with HC (P=0.0162). The frequencies of Th17 cells (CD4 + IL-17A + ) were significantly elevated in ECA patients versus HC (3.50% ± 0.33% vs 1.82% ± 0.19%, P=0.0001). Increased mRNA expression of IL-17 and ROR-γt was also observed in ECA patients compared with HC (P=0.0041 and P=0.0004, respectively), while the mRNA expression of IL-6 and tumor necrosis factor-α (TNF-α) showed significant decreases (P=0.0049 and P < 0.0001, respectively). No obvious correlations were found between the frequencies of MDSCs and Th17 cells in the peripheral blood from ECA patients(r=-0.1725, P=0.3534). Arg1 mRNA levels were positively correlated with levels of IL-6 (r=0.6404, P=0.0031) and TNF-α (r=0.7646, P=0.0001). Similarly, iNOS mRNA levels were also positively correlated with levels of IL-6 (r=0.6782, P=0.0007) and TNF-α (r=0.7633, P < 0.0001). CONCLUSION: This study reveals the relationship between circulating MDSCs and Th17 cells, which may lead to new immunotherapy approaches for ECA based on the associated metabolites and cytokines.
基金Supported by National Natural Science Foundation of China(No.81371005)
文摘· AIM: To determine the effects of rapamycin on experimental autoimmune uveoretinitis(EAU) and investigate of role of rapamycin on T cell subsets in the disease.·METHODS: EAU was induced in rats using peptides1169 to 1191 of the interphotoreceptor binding protein(IRBP). Rapamycin(0.2 mg/kg/d) was administrated by intraperitoneal injection for a consecutive 7d after immunization. Th1/Th2/Th17 cytokines, TGF-β1, and IL-6produced by lymphocyteswere measured by ELISA, while Th17 cells and CD4 +CD25 + regulatory T cells(Tregs)from rat spleen were detected by flow cytometry.·RESULTS: Intraperitoneal treatment immediately after immunization dramatically ameliorated the clinical course of EAU. Clinical responses were associated with reduced retinal inflammatory cell infiltration and tissue destruction. Rapamycin induced suppression of Th1/Th2/Th17 cytokines, including IFN-γ, IL-2, IL-17, IL-4, and IL-10 release from T lymphocytes of EAU rats, in vitro.Rapamycin also significantly increased TGF-β1production but had no effect on IL-6 productionof T lymphocytes from EAU rats in vitro. Furthermore,rapamycin decreased the ratio of Th17 cells/CD4 +T cells and upregulated Tregs in EAU, as detected by flow cytometry.·CONCLUSION: Rapamycin effectively interferes with T cell mediated autoimmune uveitis by inhibiting antigen-specific T cell functions and enhancing Tregs in EAU.Rapamycin is a promising new alternative as an adjunct corticosteroid-sparing agent for treating uveitis.
文摘AIM To investigate T-cell activation, the percentage of peripheral T regulatory cells(Tregs), Th17 cells and the circulating cytokine profile in systemic sclerosis(SSc).METHODS We enrolled a total of 24 SSc patients and 16 healthy controls in the study and divided the patients as having diffuse cutaneous SSc(dc SSc, n = 13) or limited cutaneous SSc(lc SSc, n = 11). We performed a further subdivision of the patients regarding the stage of the disease-early, intermediate or late. Peripheral venous blood samples were collected from all subjects. We performed flow cytometric analysis of the activationcapacity of T-lymphocytes upon stimulation with PHA-M and of the percentage of peripheral Tregs and Th17 cells in both patients and healthy controls. We used ELISA to quantitate serum levels of human interleukin(IL)-6, IL-10, tissue growth factor-β1(TGF-β1), and IL-17 A.RESULTS We identified a decreased percentage of CD3+CD69+ cells in PHA-stimulated samples from SSc patients in comparison with healthy controls(13.35% ± 2.90% vs 37.03% ± 2.33%, P < 0.001). However, we did not establish a correlation between the down-regulated CD3+CD69+ cells and the clinical subset, nor regarding the stage of the disease. The activated CD4+CD25+ peripheral lymphocytes were represented in decreased percentage in patients when compared to controls(6.30% ± 0.68% vs 9.36% ± 1.08%, P = 0.016). Regarding the forms of the disease, dc SSc patients demonstrated lower frequency of CD4+CD25+ T cells against healthy subjects(5.95% ± 0.89% vs 9.36% ± 1.08%, P = 0.025). With regard to Th17 cells, our patients demonstrated increased percentage in comparison with controls(18.13% ± 1.55% vs 13.73% ± 1.21%, P = 0.031). We detected up-regulated Th17 cells within the lc SSc subset against controls(20.46% ± 2.41% vs 13.73% ± 1.21%, P = 0.025), nevertheless no difference was found between dc SSc and lc SSc patients. Flow cytometric analysis revealed an increased percentage of CD4+CD25-Foxp3+ in dc SSc patients compared to controls(10.94% ± 1.65% vs 6.88% ± 0.91, P = 0.032). Regarding the peripheral cytokine profile, we detected raised levels of IL-6 [2.10(1.05-4.60) pg/m L vs 0.00 pg/m L, P < 0.001], TGF-β1(19.94 ± 3.35 ng/m L vs 10.03 ± 2.25 ng/m L, P = 0.02), IL-10(2.83 ± 0.44 pg/m L vs 0.68 ± 0.51 pg/m L, P = 0.008), and IL-17 A [6.30(2.50-15.60) pg/m L vs 0(0.00-0.05) pg/m L, P < 0.001] in patients when compared to healthy controls. Furthermore, we found increased circulating IL-10, TGF-β, IL-6 and IL-17 A in the lc SSc subset vs control subjects, as it follows: IL-10(3.32 ± 0.59 pg/m L vs 0.68 ± 0.51 pg/m L, P = 0.003), TGF-β1(22.82 ± 4.99 ng/m L vs 10.03 ± 2.25 ng/m L, P = 0.031), IL-6 [2.08(1.51-4.69) pg/m L vs 0.00 pg/m L, P < 0.001], and IL-17 A [14.50(8.55-41.65) pg/m L vs 0.00(0.00-0.05) pg/m L, P < 0.001]. Furthermore, circulating IL-17 A was higher in lc SSc as opposed to dc SSc subset(31.99 ± 13.29 pg/m L vs 7.14 ± 3.01 pg/m L, P = 0.008). Within the dc SSc subset, raised levels of IL-17 A and IL-6 were detected vs healthy controls: IL-17 A [2.60(0.45-9.80) pg/m L vs 0.00(0.00-0.05) pg/m L, P < 0.001], IL-6 [2.80(1.03-7.23) pg/m L vs 0.00 pg/m L, P < 0.001]. Regarding the stages of the disease, TGF-β1 serum levels were increased in early stage against late stage, independently from the SSc phenotype(30.03 ± 4.59 ng/m L vs 13.08 ± 4.50 ng/m L, P = 0.017).CONCLUSION It is likely that the altered percentage of Th17 and CD4+CD25-Fox P3+ cells along with the peripheral cytokine profile in patients with SSc may play a key role in the pathogenesis of the disease.
文摘Objective To explore whether age,disease severity,cytokines and lymphocytes in H1N1 influenza A patients correlate with viral load and clearance.Methods Total of 70 mild and 16 severe patients infected with H1N1 influenza A virus were enrolled in this study.Results It was found that the patients under 14 years old and severe patients displayed significantly higher viral loads and prolonged viral shedding periods compared with the patients over 14 years old and mild patients,respectively(P < 0.05).Moreover,the patients under 14 years old and severe patients displayed significantly lower Th17 cell frequency than the patients over 14 years old and mild patients(P < 0.01).The viral shedding period inversely correlated with the frequency of IL-17+IFN-γ-CD4+ T cells.Additionally,the decreased concentration of serum TGF-β correlated with the decreased frequency of IL-17+IFN-γ-CD4+ T cells.Conclusions Both younger and severe patients are associated with higher viral loads and longer viral shedding periods,which may partially be attributed to the impaired Th17 cell response.
文摘Objective: To explore the expression of IL-27, Th17 cells and CD4+CD25+ regulatory T cells (Treg) as well as its associated cytokines in peripheral blood of patients with allergic rhinitis (AR). Method: From March 2012 to May, the peripheral blood of 24 cases of AR patients (AR group) and 16 cases of healthy volunteers (control group) was collected, and the percentage of Th17 cells and Treg cells in the peripheral blood was detected by flow cytometry (FCM);the levels of IL-27, IL-17 and IL-10 in serum was detected by ELISA. Result: The percentage of Th17 cells in AR group and the control group was 1.76% ± 0.60% and 0.59% ± 0.17%, respectively. It was higher in AR group than in control group, and the difference between two groups was statistically significant (P 0.05). Conclusion: In the peripheral blood of AR patients there was a reduction of IL-27 level and imbalance of Th17/Treg cell function. IL-27 on Th17/Treg cells adjustment may play an important role on the pathogenesis of the AR.
基金This work was supported by the NIH(R01 AI160774,R01 AI123193,and R56 AG071256)the National Multiple Sclerosis Society(RG-1802-30483 to YYW)The figures were created using BioRender.com.
文摘Balanced immunity is pivotal for health and homeostasis.CD4+helper T(Th)cells are central to the balance between immune tolerance and immune rejection.Th cells adopt distinct functions to maintain tolerance and clear pathogens.Dysregulation of Th cell function often leads to maladies,including autoimmunity,inflammatory disease,cancer,and infection.Regulatory T(Treg)and Th17 cells are critical Th cell types involved in immune tolerance,homeostasis,pathogenicity,and pathogen clearance.It is therefore critical to understand how Treg and Th17 cells are regulated in health and disease.Cytokines are instrumental in directing Treg and Th17 cell function.The evolutionarily conserved TGF-β(transforming growth factor-β)cytokine superfamily is of particular interest because it is central to the biology of both Treg cells that are predominantly immunosuppressive and Th17 cells that can be proinflammatory,pathogenic,and immune regulatory.How TGF-βsuperfamily members and their intricate signaling pathways regulate Treg and Th17 cell function is a question that has been intensely investigated for two decades.Here,we introduce the fundamental biology of TGF-βsuperfamily signaling,Treg cells,and Th17 cells and discuss in detail how the TGF-βsuperfamily contributes to Treg and Th17 cell biology through complex yet ordered and cooperative signaling networks.
文摘目的探讨慢性阻塞性肺疾病急性加重期(acute exacerhation of chronic obstructive pulmonary disease,AECOPD)患者治疗前后Th17/Treg免疫平衡、呼出气一氧化氮(fraction of exhaled nitric oxide,FeNO)水平变化及对预后的影响。方法选取AECOPD患者126例,采用肺功能检测仪测定第1秒用力呼气量(forced expiratory volume in one second,FEV1)、第1秒用力呼气量占预计值百分比(FEV1%)、用力肺活量(forced vital capacity,FVC)、用力肺活量占预计值百分比(FVC%)、第1秒用力呼气量占用力肺活量的百分比(FEV1/FVC)。并使用一氧化氮测定仪检测FeNO水平,采用全身炎性反应综合征(systemic inflammaton response syndrome,SIRS)评分进行评分,采用流式细胞仪检测血清辅助性T细胞17(T help 17cells,Th17)、调节性T细胞(T Regulatory cells,Treg)水平,比较治疗前后患者肺功能指标、FeNO水平、SIRS评分、Th17/Treg水平等指标变化情况。结果治疗3个月后,AECOPD患者FEV1%、FEV1/FVC、Th17、Th17/Treg水平显著高于治疗前,FeNO、血清Treg水平、SIRS评分显著低于治疗前(P<0.05)。126例AECOPD患者治疗3个月后存活94例(74.60%);死亡32例(25.40%)。存活组FEV1%、FEV1/FVC、Treg水平显著高于死亡组,FeNO、Th17、Th17/Treg及SIRS评分显著低于死亡组(P<0.05)。多因素Logistic回归分析结果显示,治疗前FEV1%、FEV1/FVC、Treg是AECOPD患者预后的危险因素(P<0.05);FeNO、Th17、Th17/Treg、SIRS评分是AECOPD患者预后的保护因素(P<0.05)。结论AECOPD患者治疗后肺功能提高,Th17/Treg、FeNO降低,肺功能、Th17/Treg免疫平衡、FeNO水平对AECOPD患者疗效评估及预后判断具有重要意义。
基金Baoding Science and Technology Program Project(2041ZF295)Hebei University Medical Discipline Cultivation Program(2022B03)。
文摘Objective:To investigate the detection of Th17/Treg cell-related factors in patients with gestational diabetes mellitus(GDM)and its clinical significance.Methods:In this study,a retrospective cohort research method was used to collect the clinical data of 42 patients who were hospitalized in the Affiliated Hospital of Hebei University and received the diagnosis of GDM from January 2018 to December 2022,as well as 42 patients with normal pregnancies during the same period.The Th17/Treg expression levels and metabolism-related indexes in the peripheral blood of patients were detected by radioimmunoassay.Results:The relative expression of Th17 in the serum of patients in the GDM group was significantly higher than that of the control group,and the level of Treg was significantly lower than that of the control group(P<0.05);the levels of FBG,FINS,2hBG,TC,TG and HOMA-IR of the patients in the GDM group were significantly higher than that of the control group,and the level of HOMA-βwas significantly lower than that of the control group(P<0.05).Conclusion:The imbalance of the Th17/Treg cell ratio in patients with GDM may be related to their disease progression and prognosis,providing new ideas and strategies for the clinical treatment of GDM.
