III. Department of Medicine, Division of Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Sci Immunol. 2020 Aug 7;5(50). doi: 10.1126/sciimmunol.aba4163.
Although it is well established that microbial infections predispose to autoimmune diseases, the underlying mechanisms remain poorly understood. After infection, tissue-resident memory T (T) cells persist in peripheral organs and provide immune protection against reinfection. However, whether T cells participate in responses unrelated to the primary infection, such as autoimmune inflammation, is unknown. By using high-dimensional single-cell analysis, we identified CD4 T cells with a T17 signature (termed T17 cells) in kidneys of patients with ANCA-associated glomerulonephritis. Experimental models demonstrated that renal T17 cells were induced by pathogens infecting the kidney, such as , , and uropathogenic , and persisted after the clearance of infections. Upon induction of experimental glomerulonephritis, these kidney T17 cells rapidly responded to local proinflammatory cytokines by producing IL-17A and thereby exacerbate renal pathology. Thus, our data show that pathogen-induced T17 cells have a previously unrecognized function in aggravating autoimmune disease.
尽管微生物感染易患自身免疫性疾病已得到充分证实，但潜在机制仍知之甚少。感染后，组织驻留记忆 T（T）细胞在周围器官中持续存在，为再次感染提供免疫保护。然而，T 细胞是否参与与原发性感染无关的反应，如自身免疫炎症，尚不清楚。通过使用高维单细胞分析，我们在抗中性粒细胞胞质抗体相关性肾小球肾炎患者的肾脏中鉴定出具有 T17 特征的 CD4 T 细胞（称为 T17 细胞）。实验模型表明，肾脏 T17 细胞是由感染肾脏的病原体如、和尿路致病性引起的，并且在感染清除后仍然存在。在诱导实验性肾小球肾炎时，这些肾脏 T17 细胞通过产生 IL-17A 快速响应局部促炎细胞因子，从而加重肾脏病理。因此，我们的数据表明，病原体诱导的 T17 细胞在加重自身免疫性疾病方面具有以前未被认识的功能。
