Hepworth Matthew R, Fung Thomas C, Masur Samuel H, Kelsen Judith R, McConnell Fiona M, Dubrot Juan, Withers David R, Hugues Stephanie, Farrar Michael A, Reith Walter, Eberl Gérard, Baldassano Robert N, Laufer Terri M, Elson Charles O, Sonnenberg Gregory F
Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Gastroenterology Division, and Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA.
Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Gastroenterology Division, and Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Science. 2015 May 29;348(6238):1031-5. doi: 10.1126/science.aaa4812. Epub 2015 Apr 23.
Inflammatory CD4(+) T cell responses to self or commensal bacteria underlie the pathogenesis of autoimmunity and inflammatory bowel disease (IBD), respectively. Although selection of self-specific T cells in the thymus limits responses to mammalian tissue antigens, the mechanisms that control selection of commensal bacteria-specific T cells remain poorly understood. Here, we demonstrate that group 3 innate lymphoid cell (ILC3)-intrinsic expression of major histocompatibility complex class II (MHCII) is regulated similarly to thymic epithelial cells and that MHCII(+) ILC3s directly induce cell death of activated commensal bacteria-specific T cells. Further, MHCII on colonic ILC3s was reduced in pediatric IBD patients. Collectively, these results define a selection pathway for commensal bacteria-specific CD4(+) T cells in the intestine and suggest that this process is dysregulated in human IBD.
炎症性CD4(+) T细胞对自身或共生菌的反应分别是自身免疫性疾病和炎症性肠病（IBD）发病机制的基础。虽然胸腺中自身特异性T细胞的选择限制了对哺乳动物组织抗原的反应，但控制共生菌特异性T细胞选择的机制仍知之甚少。在这里，我们证明3型固有淋巴细胞（ILC3）主要组织相容性复合体II类（MHCII）的内在表达与胸腺上皮细胞的调节方式相似，并且MHCII(+) ILC3s直接诱导活化的共生菌特异性T细胞死亡。此外，儿科IBD患者结肠ILC3s上的MHCII减少。这些结果共同定义了肠道中共生菌特异性CD4(+) T细胞的选择途径，并表明该过程在人类IBD中失调。
