肠道菌群对Th17/Treg免疫平衡和炎症性肠病影响的研究进展
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摘要
炎症性肠病(inflammatory bowel disease,IBD)是一种慢性、炎症性、自身免疫性疾病,其发病机制尚未明确,目前认为是由宿主易感性基因、环境、肠道菌群等因素的综合作用引发机体异常免疫炎症应答所致。研究证明,CD4~+T细胞分化成的辅助性T细胞17(Th17)以及调节性T细胞(Treg)之间的失衡将导致IBD的发生。近期研究表明肠道菌群除直接参与IBD的发病外,部分菌群可通过分泌炎症细胞因子,或小分子物质如多糖A(polysaccharide A,PSA)、短链脂肪酸(short-chain fatty acids,SCFAs)等介导或影响Th17/Treg分化平衡,进而加重或缓解肠道免疫炎症反应,影响IBD的发病。本文就肠道菌群如何影响Th17/Treg免疫平衡及IBD的发病过程进行了梳理和总结。
Inflammatory bowel disease(IBD) is a chronic, inflammatory and autoimmune disorder, which arises as a result of the interactions of environment, flora and genetic factors leading to immunological responses and inflammation in the colon and small intestine. Studies have shown that the imbalance between Th17 and Treg differentiated from CD4~+T cells contributes to IBD. Recent studies have shown that intestinal flora, in addition to being directly involved in the pathogenesis of IBD, may mediate or influence the differentiation of Th17/Treg cells by secreting inflammatory cytokines, or small molecular substances such as polysaccharide A(PSA), short-chain fatty acids(SCFAs), thereby aggravating or alleviating the intestinal immune inflammatory response and affecting the pathogenesis of IBD. In this paper, the possible pathways of intestinal flora influencing Th17/Treg immune balance and pathogenesis of IBD will be summarized.
Inflammatory bowel disease(IBD) is a chronic, inflammatory and autoimmune disorder, which arises as a result of the interactions of environment, flora and genetic factors leading to immunological responses and inflammation in the colon and small intestine. Studies have shown that the imbalance between Th17 and Treg differentiated from CD4~+T cells contributes to IBD. Recent studies have shown that intestinal flora, in addition to being directly involved in the pathogenesis of IBD, may mediate or influence the differentiation of Th17/Treg cells by secreting inflammatory cytokines, or small molecular substances such as polysaccharide A(PSA), short-chain fatty acids(SCFAs), thereby aggravating or alleviating the intestinal immune inflammatory response and affecting the pathogenesis of IBD. In this paper, the possible pathways of intestinal flora influencing Th17/Treg immune balance and pathogenesis of IBD will be summarized.
引文
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[16]庞艳华,吴东方,马亚会,等.白细胞介素-6在溃疡性结肠炎模型小鼠Th17/Treg细胞失衡中的作用[J].胃肠病学和肝病学杂志,2018,27(5):488-491.
[17]刘揆亮,吕愈敏,顾芳.益生菌在炎症性肠病中的应用[J].世界华人消化杂志,2010,18(36):3891-3895.
[18]Tanabe S.The effect of probiotics and gut microbiota on Th17 cells[J].Int Rev Immunol,2013,32(5/6):511-525.
[19]Larmonier CB,Shehab KW,Ghishan FK,et al.Tlymphocyte dynamics in inflammatory bowel diseases:role of the microbiome[J].Biomed Res Int,2015,2015(8766):1-9.
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[21]Omenetti S,Pizarro Theresa T.The Treg/Th17 axis:Adynamic balance regulated by the gut microbiome[J].Front Immunol,2015,6:639.
[22]巫协宁,吴坚炯.克罗恩病治疗的新理念[J].胃肠病学与肝病学杂志,2018,27(5):483-487.
[23]林日添,吴维,刘占举.短链脂肪酸对肠黏膜稳态免疫调节作用的研究进展[J].免疫学杂志,2017,33(10):900-904.
[24]Carding S,Verbeke K,Vipond DT,et al.Dysbiosis of the gut microbiota in disease[J].Microb Ecol Health Dis,2015,26:1-9.
[25]De Vadder F,Kovatchevadatchary P,Goncalves D,et al.Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits[J].Cell,2014,156(1/2):84-96.
[26]Kovatcheva Datchary P,Arora T.Nutrition,the gut microbiome and the metabolic syndrome[J].Best Pract Res Clin Gastroenterol,2013,27(1):59-72.
[2]Xu M,Pokrovskii M,Ding Y,et al.c-MAF-dependent regulatory T cells mediate immunological tolerance to a gut pathobiont[J].Nature,2018,554(7692):373-377.
[3]Silva FAR,Rodrigues BL,Ayrizono MDLS,et al.The immunological basis of inflammatory bowel disease[J].Gastroenterol Res Pract,2016,2016(4):1-11.
[4]Geng X,Xue J.Expression of Treg/Th17 cells as well as related cytokines in patients with inflammatory bowel disease[J].Pak J Med Sci,2016,32(5):1164-1168.
[5]Lee GR.The balance of Th17 versus Treg Cells in autoimmunity[J].Int J Mol Sci,2018,19(3):730-744.
[6]Annie L,Leach ST,Romain B,et al.The microbiota and epigenetic regulation of T helper 17/regulatory T cells:in search of a balanced immune system[J].Front Immunol,2017,8:1-14.
[7]蒋学佩,吴小丽,黄智铭.Treg细胞和Th17细胞在炎症性肠病治疗中的作用[J].胃肠病学,2018,23(2):109-112.
[8]吴万桂,杨剑,张杰.克罗恩病患者外周血Th17、Treg比例变化及其临床意义[J].山东医药,2018,58(24):64-44.
[9]葛晓龙,曹裕,王婷婷.肠道内Th17细胞的特征及其在炎症性肠病中的作用[J].免疫学杂志,2014,30(12):1113-1117.
[10]Moschen AR,Tilg H,Raine T.IL-12,IL-23 and IL-17 in IBD:immunobiology and therapeutic targeting[J].Nat Rev Gastroenterol Hepatol,2019,16(3):1-12.
[11]顾惠琴,王超,孟政杰.Th17/Treg平衡在自身免疫性疾病中的研究进展[J].交通医学,2017,31(2):124-127.
[12]范鋆钰,刘琳.白细胞介素-25的研究进展[J].免疫学杂志,2017,33(9):89-93.
[13]陈昊,冯辉.调节性T细胞在免疫性肾病中的作用及临床应用研究进展[J].免疫学杂志,2017,33(2):93-98.
[14]王宁,金敬一,陈丽华.免疫分子对CD4+Treg的调节作用[J].免疫学杂志,2018,34(1):73-79.
[15]李佩容,危蓉,吴志平.Th17/Treg细胞及其相关细胞因子在溃疡性结肠炎发病中的作用及其研究进展[J].世界科技研究与发展,2017,39(2):194-197.
[16]庞艳华,吴东方,马亚会,等.白细胞介素-6在溃疡性结肠炎模型小鼠Th17/Treg细胞失衡中的作用[J].胃肠病学和肝病学杂志,2018,27(5):488-491.
[17]刘揆亮,吕愈敏,顾芳.益生菌在炎症性肠病中的应用[J].世界华人消化杂志,2010,18(36):3891-3895.
[18]Tanabe S.The effect of probiotics and gut microbiota on Th17 cells[J].Int Rev Immunol,2013,32(5/6):511-525.
[19]Larmonier CB,Shehab KW,Ghishan FK,et al.Tlymphocyte dynamics in inflammatory bowel diseases:role of the microbiome[J].Biomed Res Int,2015,2015(8766):1-9.
[20]Yu CG,Huang Q.Recent progress on the role of gut microbiota in the pathogenesis of inflammatory bowel disease[J].J Dig Dis,2013,14(10):513-517.
[21]Omenetti S,Pizarro Theresa T.The Treg/Th17 axis:Adynamic balance regulated by the gut microbiome[J].Front Immunol,2015,6:639.
[22]巫协宁,吴坚炯.克罗恩病治疗的新理念[J].胃肠病学与肝病学杂志,2018,27(5):483-487.
[23]林日添,吴维,刘占举.短链脂肪酸对肠黏膜稳态免疫调节作用的研究进展[J].免疫学杂志,2017,33(10):900-904.
[24]Carding S,Verbeke K,Vipond DT,et al.Dysbiosis of the gut microbiota in disease[J].Microb Ecol Health Dis,2015,26:1-9.
[25]De Vadder F,Kovatchevadatchary P,Goncalves D,et al.Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits[J].Cell,2014,156(1/2):84-96.
[26]Kovatcheva Datchary P,Arora T.Nutrition,the gut microbiome and the metabolic syndrome[J].Best Pract Res Clin Gastroenterol,2013,27(1):59-72.
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