Pathogen-induced tissue-resident memory T H 17 (T RM 17) cells amplify autoimmune kidney disease.

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 _RM ) cells persist in peripheral organs and provide immune protection against reinfection. However, whether T _RM 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 _RM cells with a T _H 17 signature (termed T _RM 17 cells) in kidneys of patients with ANCA-associated glomerulonephritis. Experimental models demonstrated that renal T _RM 17 cells were induced by pathogens infecting the kidney, such as Staphylococcus aureus , Candida albicans , and uropathogenic Escherichia coli , and persisted after the clearance of infections. Upon induction of experimental glomerulonephritis, these kidney T _RM 17 cells rapidly responded to local proinflammatory cytokines by producing IL-17A and thereby exacerbate renal pathology. Thus, our data show that pathogen-induced T _RM 17 cells have a previously unrecognized function in aggravating autoimmune disease.
(Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)