BACKGROUND Post-infectious irritable bowel syndrome(PI-IBS)is generally regarded as a functional disease.Several recent studies have reported the involvement of lowgrade inflammation and immunological dysfunction in P...BACKGROUND Post-infectious irritable bowel syndrome(PI-IBS)is generally regarded as a functional disease.Several recent studies have reported the involvement of lowgrade inflammation and immunological dysfunction in PI-IBS.T helper 17(Th17)polarization occurs in IBS.Adenosine and its receptors participate in intestinal inflammation and immune regulation.AIM To investigate the role of Th17 polarization of CD4+T cells regulated by adenosine 2A receptor(A2AR)in PI-IBS.METHODS A PI-IBS model was established by infecting mice with Trichinella spiralis.The intestinal A2AR and CD4+T lymphocytes were detected by immunohistochemistry,and the inflammatory cytokines were detected by enzyme-linked immunoassay.CD4+T lymphocytes present in the animal’s spleen were separated and cultured with or without A2AR agonist and antagonist.Western blotting and real-time quantitative polymerase chain reaction were performed to determine the effect of A2AR on the cells and intestinal tissue.Cytokine production was determined.The protein and mRNA levels of A2AR associated signaling pathway molecules were also evaluated.Furthermore,A2AR agonist and antagonist were injected into the mouse model and the clinical features were observed.RESULTS The PI-IBS mouse model showed increased expression of ATP and A2AR(P<0.05),and inhibition of A2AR improved the clinical features in PI-IBS,including the abdominal withdrawal reflex and colon transportation test(P<0.05).The number of intestinal CD4+T cells and interleukin-17(IL-17)protein levels increased during PI-IBS,which was reversed by administration of the A2AR antagonist(P<0.05).CD4+T cells expressed A2AR and produced IL-17 in vitro,which was regulated by the A2AR agonist and antagonist.The A2AR antagonist increased the production of IL-17 by CD4+T cells via the Janus kinase-signal transducer and activator of transcriptionreceptor-related orphan receptorγsignaling pathway.CONCLUSION The results of the present study suggested that the upregulation of A2AR increases PI-IBS by promoting the Th17 polarization of CD4+T cells.展开更多
目的探讨不同病因所致肝衰竭患者外周血单个核细胞(PBMCs)HLA-DR m RNA及Th17和CD4^+CD25^+Treg细胞水平的变化及其意义。方法本研究纳入肝衰竭患者50例,其中乙型肝炎肝衰竭15例,药物性肝损伤12例,酒精性肝病13例,自身免疫性肝炎10例;...目的探讨不同病因所致肝衰竭患者外周血单个核细胞(PBMCs)HLA-DR m RNA及Th17和CD4^+CD25^+Treg细胞水平的变化及其意义。方法本研究纳入肝衰竭患者50例,其中乙型肝炎肝衰竭15例,药物性肝损伤12例,酒精性肝病13例,自身免疫性肝炎10例;慢性乙型肝炎患者17例和正常人10例。采用PCR法检测PBMCs中HLA-DR m RNA水平,使用流式细胞仪检测CD4^+CD25^+Treg和Th17细胞百分比。结果乙型肝炎肝衰竭患者HLA-DR m RNA水平为(134.5±15.2),显著高于药物性肝损伤组的(17.9±1.2)、酒精性肝病组的(19.6±2.0)和自身免疫性肝炎组的[(11.2±1.2),P<0.05];不同病因肝衰竭患者Th17和CD4^+CD25^+Treg细胞百分比[分别为(4.4±0.6)%和(3.9±0.6)%左右]的差异无统计学意义(P>0.05),但与慢性乙型肝炎[分别为(3.7±0.2)%和(6.1±0.4)%和正常人(2.1±0.7)%和(7.0±0.9)%比,均有显著性差异(P<0.05);对不同病因肝衰竭患者进行动态观察发现,19例死亡患者CD4^+CD25^+Treg细胞百分比呈持续下降,直至死亡,而31例生存患者则逐渐恢复至接近正常水平。结论外周血单个核细胞HLA-DR m RNA水平及Th17和CD4^+CD25^+Treg细胞百分比的变化与肝衰竭患者的病情密切相关,可作为判断肝衰竭严重程度及预后的指标。展开更多
目的检测乙肝肝硬化患者外周血中25-(OH)D3、Th17、CD4^+Treg细胞变化,为维生素D治疗乙肝肝硬化提供依据。方法选取乙肝肝硬化患者21例,正常对照者15例,采用电化学发光免疫测定法检测25-(OH)D3水平,采用流式细胞仪检测Th17细胞、CD4^+T...目的检测乙肝肝硬化患者外周血中25-(OH)D3、Th17、CD4^+Treg细胞变化,为维生素D治疗乙肝肝硬化提供依据。方法选取乙肝肝硬化患者21例,正常对照者15例,采用电化学发光免疫测定法检测25-(OH)D3水平,采用流式细胞仪检测Th17细胞、CD4^+Treg细胞水平,并计算Th17/Treg比率。结果健康对照组外周血25-(OH)D3为(31.87±5.97)ng/ml,乙肝肝硬化组25-(OH)D3明显降低,为(11.89±6.04)ng/ml,两者相比差异具有统计学意义(t=9.510,P=0.001)。与健康对照组相比,乙肝肝硬化组外周血Th17细胞百分比(0.913%±0.216%vs 2.498%±2.583%)增高,CD4^+Treg细胞百分比降低(3.964%±1.116%vs 2.333%±1.714%),Th17/Treg比率(1.199±0.973 vs 0.256±0.138)增高,差异均有统计学意义(P<0.05)。结论乙肝肝硬化患者外周血25-(OH)D3水平显著降低,Th17增高,CD4^+Treg降低,存在CD4^+Treg、Th17、Treg/Th17免疫平衡紊乱,增加外周血25-(OH)D3水平有可能调节乙肝肝硬化患者体内CD4^+Treg、Th17、Treg/Th17变化,改变其免疫状态。展开更多
基金Supported by National Natural Science Foundation of China,No.81160057,No.81860102,and No.82060102.
文摘BACKGROUND Post-infectious irritable bowel syndrome(PI-IBS)is generally regarded as a functional disease.Several recent studies have reported the involvement of lowgrade inflammation and immunological dysfunction in PI-IBS.T helper 17(Th17)polarization occurs in IBS.Adenosine and its receptors participate in intestinal inflammation and immune regulation.AIM To investigate the role of Th17 polarization of CD4+T cells regulated by adenosine 2A receptor(A2AR)in PI-IBS.METHODS A PI-IBS model was established by infecting mice with Trichinella spiralis.The intestinal A2AR and CD4+T lymphocytes were detected by immunohistochemistry,and the inflammatory cytokines were detected by enzyme-linked immunoassay.CD4+T lymphocytes present in the animal’s spleen were separated and cultured with or without A2AR agonist and antagonist.Western blotting and real-time quantitative polymerase chain reaction were performed to determine the effect of A2AR on the cells and intestinal tissue.Cytokine production was determined.The protein and mRNA levels of A2AR associated signaling pathway molecules were also evaluated.Furthermore,A2AR agonist and antagonist were injected into the mouse model and the clinical features were observed.RESULTS The PI-IBS mouse model showed increased expression of ATP and A2AR(P<0.05),and inhibition of A2AR improved the clinical features in PI-IBS,including the abdominal withdrawal reflex and colon transportation test(P<0.05).The number of intestinal CD4+T cells and interleukin-17(IL-17)protein levels increased during PI-IBS,which was reversed by administration of the A2AR antagonist(P<0.05).CD4+T cells expressed A2AR and produced IL-17 in vitro,which was regulated by the A2AR agonist and antagonist.The A2AR antagonist increased the production of IL-17 by CD4+T cells via the Janus kinase-signal transducer and activator of transcriptionreceptor-related orphan receptorγsignaling pathway.CONCLUSION The results of the present study suggested that the upregulation of A2AR increases PI-IBS by promoting the Th17 polarization of CD4+T cells.
文摘目的探讨不同病因所致肝衰竭患者外周血单个核细胞(PBMCs)HLA-DR m RNA及Th17和CD4^+CD25^+Treg细胞水平的变化及其意义。方法本研究纳入肝衰竭患者50例,其中乙型肝炎肝衰竭15例,药物性肝损伤12例,酒精性肝病13例,自身免疫性肝炎10例;慢性乙型肝炎患者17例和正常人10例。采用PCR法检测PBMCs中HLA-DR m RNA水平,使用流式细胞仪检测CD4^+CD25^+Treg和Th17细胞百分比。结果乙型肝炎肝衰竭患者HLA-DR m RNA水平为(134.5±15.2),显著高于药物性肝损伤组的(17.9±1.2)、酒精性肝病组的(19.6±2.0)和自身免疫性肝炎组的[(11.2±1.2),P<0.05];不同病因肝衰竭患者Th17和CD4^+CD25^+Treg细胞百分比[分别为(4.4±0.6)%和(3.9±0.6)%左右]的差异无统计学意义(P>0.05),但与慢性乙型肝炎[分别为(3.7±0.2)%和(6.1±0.4)%和正常人(2.1±0.7)%和(7.0±0.9)%比,均有显著性差异(P<0.05);对不同病因肝衰竭患者进行动态观察发现,19例死亡患者CD4^+CD25^+Treg细胞百分比呈持续下降,直至死亡,而31例生存患者则逐渐恢复至接近正常水平。结论外周血单个核细胞HLA-DR m RNA水平及Th17和CD4^+CD25^+Treg细胞百分比的变化与肝衰竭患者的病情密切相关,可作为判断肝衰竭严重程度及预后的指标。
文摘目的检测乙肝肝硬化患者外周血中25-(OH)D3、Th17、CD4^+Treg细胞变化,为维生素D治疗乙肝肝硬化提供依据。方法选取乙肝肝硬化患者21例,正常对照者15例,采用电化学发光免疫测定法检测25-(OH)D3水平,采用流式细胞仪检测Th17细胞、CD4^+Treg细胞水平,并计算Th17/Treg比率。结果健康对照组外周血25-(OH)D3为(31.87±5.97)ng/ml,乙肝肝硬化组25-(OH)D3明显降低,为(11.89±6.04)ng/ml,两者相比差异具有统计学意义(t=9.510,P=0.001)。与健康对照组相比,乙肝肝硬化组外周血Th17细胞百分比(0.913%±0.216%vs 2.498%±2.583%)增高,CD4^+Treg细胞百分比降低(3.964%±1.116%vs 2.333%±1.714%),Th17/Treg比率(1.199±0.973 vs 0.256±0.138)增高,差异均有统计学意义(P<0.05)。结论乙肝肝硬化患者外周血25-(OH)D3水平显著降低,Th17增高,CD4^+Treg降低,存在CD4^+Treg、Th17、Treg/Th17免疫平衡紊乱,增加外周血25-(OH)D3水平有可能调节乙肝肝硬化患者体内CD4^+Treg、Th17、Treg/Th17变化,改变其免疫状态。
