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Control of T_H17 cells occurs in the small intestine

机译:T_H17细胞的控制发生在小肠中

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摘要

Interleukin (IL)-17-producing T helper cells (T_H17) are a recently identified CD4+ T cell subset distinct from T helper type 1 (T_H1) and T helper type 2 (T_H2) cells1. T_H17 cells can drive antigen-specific autoimmune diseases and are considered the main population of pathogenic T cells driving experimental autoimmune encephalomyelitis (EAE)2, the mouse model for multiple sclerosis. The factors that are needed for the generation of T_H17 cells have been well characterized3"6. However, where and how the immune system controls T_H17 cells in vivo remains unclear. Here, by using a model of tolerance induced by CD3-specific antibody, a model of sepsis and influenza A viral infection (H1N1), we show that pro-inflammatory T_H17 cells can be redirected to and controlled in the small intestine. T_H17-specific IL-17A secretion induced expression of the chemokine CCL20 in the small intestine, facilitating the migration of these cells specifically to the small intestine via the CCR6/CCL20 axis. Moreover, we found that T_H17 cells are controlled by two different mechanisms in the small intestine: first, they are eliminated via the intestinal lumen; second, pro-inflammatory T_H17 cells simultaneously acquire a regulatory phenotype with in vitro and in vivo immune-suppressive properties (rT_H17). These results identify mechanisms limiting T_H17 cell pathogenicity and implicate the gastrointestinal tract as a site for control of T_H17 cells.
机译:产生白介素(IL)-17的T辅助细胞(T_H17)是最近鉴定出的CD4 + T细胞子集,与T辅助1型(T_H1)和T辅助2型(T_H2)细胞不同。 T_H17细胞可以驱动抗原特异性自身免疫性疾病,被认为是驱动实验性自身免疫性脑脊髓炎(EAE)2(多发性硬化症的小鼠模型)的致病性T细胞的主要种群。已经充分表征了产生T_H17细胞所需的因素3“ 6。但是,免疫系统在体内何处以及如何控制T_H17细胞尚不清楚。这里,通过使用由CD3特异性抗体诱导的耐受性模型,败血症和A型流感病毒感染(H1N1)的模型,我们证明促炎性T_H17细胞可以重定向到小肠并在小肠中控制T_H17特异性IL-17A分泌诱导小肠趋化因子CCL20的表达,从而促进这些细胞通过CCR6 / CCL20轴专门迁移到小肠,此外,我们发现T_H17细胞在小肠中受两种不同的机制控制:第一,它们通过肠腔被清除;第二,促炎性T_H17细胞同时获得具有体外和体内免疫抑制特性的调节表型(rT_H17),这些结果确定了限制T_H17细胞致病性的机制并暗示胃肠道作为控制T_H17细胞的部位。

著录项

  • 来源
    《Nature》 |2011年第7357期|p.514-518|共5页
  • 作者单位

    Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA,German Rheumatism Research Center (DRFZ), A Leibniz Institute, Berlin 10117, Germany,Cluster of Excellence NeuroCure, Charite-Universitatsmedizin Berlin, Berlin 10117, Germany;

    Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA,I. Medizinische Klinik, Universitatsklinikum Hamburg-Eppendorf, Hamburg20246, Germany;

    San Raffaele Diabetes Research Institute (HSR-DRI), Milan 20132, Italy;

    German Rheumatism Research Center (DRFZ), A Leibniz Institute, Berlin 10117, Germany;

    Departments of Biomedical Sciences and Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA,Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90048, USA;

    Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, The University of North Carolina, School of Medicine, Chapel Hill, North Carolina 27599, USA;

    Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA;

    Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA;

    Department of Molecular Cell Biology, Faculty of Medicine, Vrije Universiteit, Amsterdam, 1081 BT, The Netherlands;

    Departmentof Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA;

    Centerfor Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan;

    Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA;

    Department of Genetics, LSU Health Sciences Center, New Orleans, Louisiana 70112, USA;

    Diabetes Center at the University of California San Francisco, San Francisco, California 94143, USA;

    Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA;

    Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA,Howard Hughes Medical Institute, New Haven;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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