Pathogen-induced tissue-resident memory TH17 (TRM17) cells amplify autoimmune kidney disease.

Abstract

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_H17 signature (termed T_RM17 cells) in kidneys of patients with ANCA-associated glomerulonephritis. Experimental models demonstrated that renal T_RM17 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_RM17 cells rapidly responded to local proinflammatory cytokines by producing IL-17A and thereby exacerbate renal pathology. Thus, our data show that pathogen-induced T_RM17 cells have a previously unrecognized function in aggravating autoimmune disease.