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

Krebs, Christian F.; Reimers, Daniel; Zhao, Yu; Paust, Hans-Joachim; Bartsch, Patricia; Nunez, Sarah; Rosemblatt, Mariana, V; Hellmig, Malte; Kilian, Christoph; Borchers, Alina; Enk, Leon U. B.; Zinke, Michael; Becker, Martina; Schmid, Joanna; Klinge, Stefanie; et. al.


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.

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Título según WOS: Pathogen-induced tissue-resident memory T(H)17 (T(RM)17) cells amplify autoimmune kidney disease
Título de la Revista: SCIENCE IMMUNOLOGY
Volumen: 5
Número: 50
Fecha de publicación: 2020


Notas: ISI