Chappert Pascal
Laboratory of Cellular and Molecular Immunology; National Institute of Allergy and Infectious Diseases, NIH; Bethesda, MD, USA.
Gut Microbes. 2014 Mar-Apr;5(2):259-64. doi: 10.4161/gmic.28134. Epub 2014 Feb 6.
A key role for segmented filamentous bacteria (SFB) has recently been demonstrated in several mouse models of autoimmune diseases, including autoimmune arthritis and multiple sclerosis. The mechanism governing the activation of systemic autoreactive T cell responses by such commensals in the gut, however, remained elusive. In this addendum, we discuss recent results addressing the local regulation of autoreactive T cell sensitivity by these unique bacteria. We found that the presence of SFB in the gut microbiota was sufficient to promote a local inflammatory microenvironment altering the T cell-intrinsic desensitization process normally occurring in response to chronic self-antigen stimulation. In the absence of this key tolerance checkpoint, sustained chronic T cell proliferation, IFNγ production, and B cell activation eventually led to the development of enhanced pathologies in a Th1-driven T cell-transfer model of autoimmune arthritis.
最近在几种自身免疫性疾病的小鼠模型中，包括自身免疫性关节炎和多发性硬化症，已证明分节丝状细菌（SFB）发挥了关键作用。然而，这类共生菌在肠道中激活全身性自身反应性T细胞反应的机制仍不清楚。在本附录中，我们讨论了关于这些独特细菌对自身反应性T细胞敏感性的局部调节的最新研究结果。我们发现，肠道微生物群中SFB的存在足以促进局部炎症微环境，改变通常在慢性自身抗原刺激下发生的T细胞内在脱敏过程。在缺乏这一关键耐受检查点的情况下，持续的慢性T细胞增殖、IFNγ产生和B细胞活化最终导致在自身免疫性关节炎的Th1驱动的T细胞转移模型中病情加重。
