Inflammatory bowel disease (IBD) results from a complex series of interactions between susceptibility genes, the environment, and the immune system. The host microbiome, as well as viruses and fungi, play important ro...Inflammatory bowel disease (IBD) results from a complex series of interactions between susceptibility genes, the environment, and the immune system. The host microbiome, as well as viruses and fungi, play important roles in the development of IBD either by causing inflammation directly or indirectly through an altered immune system. New technologies have allowed researchers to be able to quantify the various components of the microbiome, which will allow for future developments in the etiology of IBD. Various components of the mucosal immune system are implicated in the pathogenesis of IBD and include intestinal epithelial cells, innate lymphoid cells, cells of the innate (macrophages/monocytes, neutrophils, and dendritic cells) and adaptive (T-cells and B-cells) immune system, and their secreted mediators (cytokines and chemokines). Either a mucosal susceptibility or defect in sampling of gut luminal antigen, possibly through the process of autophagy, leads to activation of innate immune response that may be mediated by enhanced toll-like receptor activity. The antigen presenting cells then mediate the differentiation of naïve T-cells into effector T helper (Th) cells, including Th1, Th2, and Th17, which alter gut homeostasis and lead to IBD. In this review, the effects of these components in the immunopathogenesis of IBD will be discussed.展开更多
IL-22 is a novel cytokine in the IL-10 family that functions to promote innate immunity of tissues against infection. Although CD4＋ helper T lymphocytes （TH） were found as a source of IL-22, the regulation of this ...IL-22 is a novel cytokine in the IL-10 family that functions to promote innate immunity of tissues against infection. Although CD4＋ helper T lymphocytes （TH） were found as a source of IL-22, the regulation of this cytokine has been poorly understood. Here, we show that IL-22 is expressed at both mRNA and protein levels by a novel subset of TH cells that also makes IL-17. IL-22 and IL-17 were found to be coordinately regulated by TGFI3 and IL-6 during TH differentiation by real-time PCR as well as ELISA analysis. However, IL-22 does not regulate TH differentiation; exogenous IL-22 or an IL-22 antagonist had no effect on TH differentiation. These data demonstrate a novel cytokine expressed by IL-17-producing T cells, and suggest interaction and synergy of IL-22 and IL-l 7 signaling pathways in tissue inflammation and autoimmune diseases.展开更多
Inflammatory bowel disease (IBD) includes Crohn's disease and ulcerative colitis. The exact etiology and pathology of IBD remain unknown. Available evidence suggests that an abnormal immune response against the mi...Inflammatory bowel disease (IBD) includes Crohn's disease and ulcerative colitis. The exact etiology and pathology of IBD remain unknown. Available evidence suggests that an abnormal immune response against the microorganisms in the intestine is responsible for the disease in genetically susceptible individuals. Dysregulation of immune response in the intestine plays a critical role in the pathogenesis of IBD, involving a wide range of molecules including cytokines. On the other hand, besides T helper (Th) 1 and Th2 cell immune responses, other subsets of T cells, namely Th17 and regulatory T cells, are likely associated with disease progression. Studying the interactions between various constituents of the innate and adaptive immune systems will certainly open new horizons of the knowledge about the immunologic mechanisms in IBD. (c) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.展开更多
AIM To investigate the role of regulatory T cell(Treg) subsets in the balance between Treg and T helper 17(Th17) cells in various tissues from mice with dextran sulfate sodium-induced colitis.METHODS T r e g c e l l s...AIM To investigate the role of regulatory T cell(Treg) subsets in the balance between Treg and T helper 17(Th17) cells in various tissues from mice with dextran sulfate sodium-induced colitis.METHODS T r e g c e l l s, T r e g c e l l s u b s e t s, T h 1 7 c e l l s, a n d CD4+CD25+FoxP 3+IL-17+ cells from the lamina propria of colon(LPC) and other ulcerative colitis(UC) mouse tissues were evaluated by flow cytometry. Forkhead box protein 3(FoxP 3), interleukin 17A(IL-17A), and RORC m RNA levels were assessed by real-time PCR, while interleukin-10(IL-10) and IL-17 A levels were detected with a Cytometric Beads Array.RESULTS In peripheral blood monocytes(PBMC), mesenteric lymphnode(MLN), lamina propria of jejunum(LPJ) and LPC from UC mice, Treg cell numbers were increased(P < 0.05), and FoxP 3 and IL-10 mR NA levels were decreased. Th17 cell numbers were also increased in PBMC and LPC, as were IL-17 A levels in PBMC, LPJ, and serum. The number of FrI subset cells(CD4+CD45RA+FoxP 3low) was increased in the spleen, MLN, LPJ, and LPC. FrI I subset cells(CD4+CD45RA-Fox P3high) were decreased among PBMC, MLN, LPJ, and LPC, but the number of Fr III cells(CD4+CD45RA-FoxP 3low) and CD4+CD25+FoxP 3+IL-17A+ cells was increased. Fox P3 m RNA levels in CD4+CD45RA-Fox P3 low cells decreased in PBMC, MLN, LPJ, and LPC in UC mice, while IL-17 A and RORC mR NA increased. In UC mice the distribution of Treg, Th17 cells, CD4+CD45RA-FoxP 3high, and CD4+CD45RA-FoxP 3low cells was higher in LPC relative to other tissues.CONCLUSION Increased numbers of CD4+CD45RA-FoxP 3low cells may cause an imbalance between Treg and Th17 cells that is mainly localized to the LPC rather than secondary lymphoid tissues.展开更多
AIM:To investigate the impact of different anesthetic techniques on T-helper(Th) cell subsets in hepatocellular carcinoma(HCC) patients undergoing hepatectomy.METHODS:Sixty-one HCC patients who received hepatectomies ...AIM:To investigate the impact of different anesthetic techniques on T-helper(Th) cell subsets in hepatocellular carcinoma(HCC) patients undergoing hepatectomy.METHODS:Sixty-one HCC patients who received hepatectomies were randomized into an epidural combined general anesthesia(G + E;n = 31) or a general anesthesia(G;n = 30) group.Blood samples were obtained the morning before the operation(d0),and on the second(d2) and seventh(d7) day after the operation.Th cell contents were evaluated using flow cytometry,realtime reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay.RESULTS:In all 61 patients,Th1 and Th2 cell frequencies,and interferon-(IFN-) mRNA expression markedly increased on d2,compared to d0.They recovered slightly on d7,and the Th1/Th2 ratio increased markedly on d7,compared with d2.In contrast,Th17,regulatory T cell(Treg),and interleukin-17(IL-17) levels and FOXP3 mRNA expression showed no significant change on d2,and then markedly decreased on d7.Similarly,plasma IFN-concentration on d2 was much higher than that on d0,and then partly recovered on d7.As compared with the G group,in the G + E group,Th1 cell frequencies and the Th1/Th2 ratio were slightly higher on d2 and significantly higher on d7,while Th2,Th17,and Treg cell frequencies were slightly lower on d2,and significantly lower on d7.Consistently,on d7,IFN-mRNA and protein levels and the IFN-/IL-4 ratio in the G + E group were higher than those in the G group.In contrast,the IL-17 mRNA level,and IL-17 and transforming growth factor-1 concentrations in the G + E group were lower than those in the G group.CONCLUSION:G + E is superior to G in shifting the Th1/Th2 balance towards Th1,while decreasing Th17 and Treg,potentially benefiting HCC patients by promoting anti-tumor Th polarization.展开更多
目的了解砷暴露后大鼠肝脏中辅助性T细胞-17（Thelper17，Th17）、调节性T细胞（regulatory T cell，Treg）的浸润情况，探讨Th17与Treg细胞浸润在砷致大鼠肝脏免疫损伤中的作用。方法选取健康初断乳Wistar大鼠32只，雌雄各半，按体质量...目的了解砷暴露后大鼠肝脏中辅助性T细胞-17（Thelper17，Th17）、调节性T细胞（regulatory T cell，Treg）的浸润情况，探讨Th17与Treg细胞浸润在砷致大鼠肝脏免疫损伤中的作用。方法选取健康初断乳Wistar大鼠32只，雌雄各半，按体质量（80～100g）采用随机数字表法分为对照组，低、中、高砷剂量组，每组8只。对照组给予去离子水灌胃，染砷各组按体质量用2．00g/L的亚砷酸钠（NaAsO2）水溶液进行灌胃，灌胃量依次为1．25、2．50、5．00ml／kg，每周6d，染砷时间持续4个月。4个月后处死大鼠，取大鼠肝脏组织，采用电感耦合等离子体质谱仪（ICP-MS）检测肝砷含量；苏木精．伊红染色（HE）观察大鼠肝脏组织形态学变化情况；免疫组织化学方法检测肝脏组织白细胞介素（IL）-17A（Th17细胞分泌的炎性因子）、叉头翼状螺旋因子3（Foxp3，Treg细胞的谱系特异性转录因子）蛋白表达情况。结果①低、中、高砷剂量组肝砷含量[中位数（四分位数）：63．83（52．79—80．26）、59．16（51．38—76．58）、79．26（69．59～107．44）μg／g]高于对照组[2．86（1．76—3．56）μg／g，P均〈0．05]，且高砷剂量组高于中砷剂量组（P〈0．05）。（2）随大鼠染砷剂量的增加，肝脏组织中炎细胞数增加，高砷剂量组大鼠肝脏组织呈现空泡样变，部分区域有点状坏死等病理改变。③与对照组，低、中砷剂量组比较（0．001±0．001、0．010±0．020、0．030±0．080）。高砷剂量组IL-17A蛋白在肝脏组织中的表达（0．220±0．130）均显著增高（P均〈0．05），组间比较差异有统计学意义（F=14．776，P〈0．05）；低、中、高砷剂量组Foxp3蛋白表达量（0．270±0．050、0．330±0．040、0．320±0．070）高于对照组（0．070±0．020），组间比较差异有统计学意义（F=56．990，P〈0．05）。④大鼠肝砷含量与肝脏组�展开更多
基金Supported by NIH KO8 DK093578CCFA Career Development Award 3467(DQS)F Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute
文摘Inflammatory bowel disease (IBD) results from a complex series of interactions between susceptibility genes, the environment, and the immune system. The host microbiome, as well as viruses and fungi, play important roles in the development of IBD either by causing inflammation directly or indirectly through an altered immune system. New technologies have allowed researchers to be able to quantify the various components of the microbiome, which will allow for future developments in the etiology of IBD. Various components of the mucosal immune system are implicated in the pathogenesis of IBD and include intestinal epithelial cells, innate lymphoid cells, cells of the innate (macrophages/monocytes, neutrophils, and dendritic cells) and adaptive (T-cells and B-cells) immune system, and their secreted mediators (cytokines and chemokines). Either a mucosal susceptibility or defect in sampling of gut luminal antigen, possibly through the process of autophagy, leads to activation of innate immune response that may be mediated by enhanced toll-like receptor activity. The antigen presenting cells then mediate the differentiation of naïve T-cells into effector T helper (Th) cells, including Th1, Th2, and Th17, which alter gut homeostasis and lead to IBD. In this review, the effects of these components in the immunopathogenesis of IBD will be discussed.
文摘IL-22 is a novel cytokine in the IL-10 family that functions to promote innate immunity of tissues against infection. Although CD4＋ helper T lymphocytes （TH） were found as a source of IL-22, the regulation of this cytokine has been poorly understood. Here, we show that IL-22 is expressed at both mRNA and protein levels by a novel subset of TH cells that also makes IL-17. IL-22 and IL-17 were found to be coordinately regulated by TGFI3 and IL-6 during TH differentiation by real-time PCR as well as ELISA analysis. However, IL-22 does not regulate TH differentiation; exogenous IL-22 or an IL-22 antagonist had no effect on TH differentiation. These data demonstrate a novel cytokine expressed by IL-17-producing T cells, and suggest interaction and synergy of IL-22 and IL-l 7 signaling pathways in tissue inflammation and autoimmune diseases.
基金Supported by Grants from the National Natural Science Foundation of China,No.81061120521 and No.81270470Shanghai Science and Technology Commission,No.12XD1404000
文摘Inflammatory bowel disease (IBD) includes Crohn's disease and ulcerative colitis. The exact etiology and pathology of IBD remain unknown. Available evidence suggests that an abnormal immune response against the microorganisms in the intestine is responsible for the disease in genetically susceptible individuals. Dysregulation of immune response in the intestine plays a critical role in the pathogenesis of IBD, involving a wide range of molecules including cytokines. On the other hand, besides T helper (Th) 1 and Th2 cell immune responses, other subsets of T cells, namely Th17 and regulatory T cells, are likely associated with disease progression. Studying the interactions between various constituents of the innate and adaptive immune systems will certainly open new horizons of the knowledge about the immunologic mechanisms in IBD. (c) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.
基金Supported by the National Natural Science Foundation of China,No.81300294State Scholarship Fund of China,No.201509110033
文摘AIM To investigate the role of regulatory T cell(Treg) subsets in the balance between Treg and T helper 17(Th17) cells in various tissues from mice with dextran sulfate sodium-induced colitis.METHODS T r e g c e l l s, T r e g c e l l s u b s e t s, T h 1 7 c e l l s, a n d CD4+CD25+FoxP 3+IL-17+ cells from the lamina propria of colon(LPC) and other ulcerative colitis(UC) mouse tissues were evaluated by flow cytometry. Forkhead box protein 3(FoxP 3), interleukin 17A(IL-17A), and RORC m RNA levels were assessed by real-time PCR, while interleukin-10(IL-10) and IL-17 A levels were detected with a Cytometric Beads Array.RESULTS In peripheral blood monocytes(PBMC), mesenteric lymphnode(MLN), lamina propria of jejunum(LPJ) and LPC from UC mice, Treg cell numbers were increased(P < 0.05), and FoxP 3 and IL-10 mR NA levels were decreased. Th17 cell numbers were also increased in PBMC and LPC, as were IL-17 A levels in PBMC, LPJ, and serum. The number of FrI subset cells(CD4+CD45RA+FoxP 3low) was increased in the spleen, MLN, LPJ, and LPC. FrI I subset cells(CD4+CD45RA-Fox P3high) were decreased among PBMC, MLN, LPJ, and LPC, but the number of Fr III cells(CD4+CD45RA-FoxP 3low) and CD4+CD25+FoxP 3+IL-17A+ cells was increased. Fox P3 m RNA levels in CD4+CD45RA-Fox P3 low cells decreased in PBMC, MLN, LPJ, and LPC in UC mice, while IL-17 A and RORC mR NA increased. In UC mice the distribution of Treg, Th17 cells, CD4+CD45RA-FoxP 3high, and CD4+CD45RA-FoxP 3low cells was higher in LPC relative to other tissues.CONCLUSION Increased numbers of CD4+CD45RA-FoxP 3low cells may cause an imbalance between Treg and Th17 cells that is mainly localized to the LPC rather than secondary lymphoid tissues.
基金Supported by The State 863 High Technology R and D Project of China,No.2007AA02Z479National Natural Science Foundation of China,No.30972949+3 种基金Shanghai Rising-Star Program, No.10QA1401300FANEDD,No.201183Science and Technology Commission of Shanghai Municipality,No.114119a4400Shanghai "Chen Guang" Project,No.11CG02
文摘AIM:To investigate the impact of different anesthetic techniques on T-helper(Th) cell subsets in hepatocellular carcinoma(HCC) patients undergoing hepatectomy.METHODS:Sixty-one HCC patients who received hepatectomies were randomized into an epidural combined general anesthesia(G + E;n = 31) or a general anesthesia(G;n = 30) group.Blood samples were obtained the morning before the operation(d0),and on the second(d2) and seventh(d7) day after the operation.Th cell contents were evaluated using flow cytometry,realtime reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay.RESULTS:In all 61 patients,Th1 and Th2 cell frequencies,and interferon-(IFN-) mRNA expression markedly increased on d2,compared to d0.They recovered slightly on d7,and the Th1/Th2 ratio increased markedly on d7,compared with d2.In contrast,Th17,regulatory T cell(Treg),and interleukin-17(IL-17) levels and FOXP3 mRNA expression showed no significant change on d2,and then markedly decreased on d7.Similarly,plasma IFN-concentration on d2 was much higher than that on d0,and then partly recovered on d7.As compared with the G group,in the G + E group,Th1 cell frequencies and the Th1/Th2 ratio were slightly higher on d2 and significantly higher on d7,while Th2,Th17,and Treg cell frequencies were slightly lower on d2,and significantly lower on d7.Consistently,on d7,IFN-mRNA and protein levels and the IFN-/IL-4 ratio in the G + E group were higher than those in the G group.In contrast,the IL-17 mRNA level,and IL-17 and transforming growth factor-1 concentrations in the G + E group were lower than those in the G group.CONCLUSION:G + E is superior to G in shifting the Th1/Th2 balance towards Th1,while decreasing Th17 and Treg,potentially benefiting HCC patients by promoting anti-tumor Th polarization.
文摘目的了解砷暴露后大鼠肝脏中辅助性T细胞-17（Thelper17，Th17）、调节性T细胞（regulatory T cell，Treg）的浸润情况，探讨Th17与Treg细胞浸润在砷致大鼠肝脏免疫损伤中的作用。方法选取健康初断乳Wistar大鼠32只，雌雄各半，按体质量（80～100g）采用随机数字表法分为对照组，低、中、高砷剂量组，每组8只。对照组给予去离子水灌胃，染砷各组按体质量用2．00g/L的亚砷酸钠（NaAsO2）水溶液进行灌胃，灌胃量依次为1．25、2．50、5．00ml／kg，每周6d，染砷时间持续4个月。4个月后处死大鼠，取大鼠肝脏组织，采用电感耦合等离子体质谱仪（ICP-MS）检测肝砷含量；苏木精．伊红染色（HE）观察大鼠肝脏组织形态学变化情况；免疫组织化学方法检测肝脏组织白细胞介素（IL）-17A（Th17细胞分泌的炎性因子）、叉头翼状螺旋因子3（Foxp3，Treg细胞的谱系特异性转录因子）蛋白表达情况。结果①低、中、高砷剂量组肝砷含量[中位数（四分位数）：63．83（52．79—80．26）、59．16（51．38—76．58）、79．26（69．59～107．44）μg／g]高于对照组[2．86（1．76—3．56）μg／g，P均〈0．05]，且高砷剂量组高于中砷剂量组（P〈0．05）。（2）随大鼠染砷剂量的增加，肝脏组织中炎细胞数增加，高砷剂量组大鼠肝脏组织呈现空泡样变，部分区域有点状坏死等病理改变。③与对照组，低、中砷剂量组比较（0．001±0．001、0．010±0．020、0．030±0．080）。高砷剂量组IL-17A蛋白在肝脏组织中的表达（0．220±0．130）均显著增高（P均〈0．05），组间比较差异有统计学意义（F=14．776，P〈0．05）；低、中、高砷剂量组Foxp3蛋白表达量（0．270±0．050、0．330±0．040、0．320±0．070）高于对照组（0．070±0．020），组间比较差异有统计学意义（F=56．990，P〈0．05）。④大鼠肝砷含量与肝脏组�
