Department of Immunobiology, University of Arizona, Tucson, AZ 85719, USA.
Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
Cell Host Microbe. 2017 Nov 8;22(5):697-704.e4. doi: 10.1016/j.chom.2017.10.007.
Lung complications are a major cause of rheumatoid arthritis-related mortality. Involvement of gut microbiota in lung diseases by the gut-lung axis has been widely observed, but the underlying mechanism remains mostly unknown. Using an autoimmune arthritis model, we show that a constituent of the gut microbiota, segmented filamentous bacteria (SFB), distantly provoke lung pathology. SFB induce autoantibodies in lung during the pre-arthritic phase, and SFB-dependent lung pathology requires the T helper 17 (Th17) responses. SFB-induced gut Th17 cells are preferentially recruited to lung over spleen due to robust expression in the lung of the Th17 chemoattractant, CCL20. Additionally, we found that in peripheral tissues, SFB selectively expand dual T cell receptor (TCR)-expressing Th17 cells recognizing both an SFB epitope and self-antigen, thus augmenting autoimmunity. This study reveals mechanisms for commensal-mediated gut-lung crosstalk and dual TCR-based autoimmunity.
肺部并发症是类风湿关节炎相关死亡率的主要原因。通过肠-肺轴，肠道微生物群与肺部疾病的关系已被广泛观察到，但潜在机制在很大程度上仍不清楚。本研究使用一种自身免疫性关节炎模型，表明肠道微生物群的一种成分，即分段丝状菌（SFB），会间接引发肺部病理。在关节炎前期，SFB 会在肺部诱导自身抗体，并且 SFB 依赖性的肺部病理需要辅助性 T 细胞 17（Th17）反应。由于肺部表达大量 Th17 趋化因子 CCL20，SFB 诱导的肠道 Th17 细胞优先募集到肺部，而不是脾脏。此外，我们发现，在周围组织中，SFB 选择性地扩增了同时表达两种 T 细胞受体（TCR）的 Th17 细胞，这些细胞既识别 SFB 表位又识别自身抗原，从而增强了自身免疫。本研究揭示了共生菌介导的肠-肺串扰和基于双重 TCR 的自身免疫的机制。
