1. Pathogen-induced tissue-resident memory TH17 (TRM17) cells amplify autoimmune kidney disease.
- Author
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Huber T.B., Franzenburg S., Koch-Nolte F., Turner J.-E., Riedel J.-H., Huber S., Gagliani N., Wiech T., Rohde H., Bono M.R., Bonn S., Panzer U., Mittrucker H.-W., Krebs C.F., Reimers D., Zhao Y., Paust H.-J., Bartsch P., Nunez S., Rosemblatt M.V., Hellmig M., Kilian C., Borchers A., Enk L.U.B., Zinke M., Becker M., Schmid J., Klinge S., Wong M.N., Puelles V.G., Schmidt C., Bertram T., Stumpf N., Hoxha E., Meyer-Schwesinger C., Lindenmeyer M.T., Cohen C.D., Rink M., Kurts C., Huber T.B., Franzenburg S., Koch-Nolte F., Turner J.-E., Riedel J.-H., Huber S., Gagliani N., Wiech T., Rohde H., Bono M.R., Bonn S., Panzer U., Mittrucker H.-W., Krebs C.F., Reimers D., Zhao Y., Paust H.-J., Bartsch P., Nunez S., Rosemblatt M.V., Hellmig M., Kilian C., Borchers A., Enk L.U.B., Zinke M., Becker M., Schmid J., Klinge S., Wong M.N., Puelles V.G., Schmidt C., Bertram T., Stumpf N., Hoxha E., Meyer-Schwesinger C., Lindenmeyer M.T., Cohen C.D., Rink M., and Kurts C.
- 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 (TRM) cells persist in peripheral organs and provide immune protection against reinfection. However, whether TRM 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+ TRM cells with a TH17 signature (termed TRM17 cells) in kidneys of patients with ANCA-associated glomerulonephritis. Experimental models demonstrated that renal TRM17 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 TRM17 cells rapidly responded to local proinflammatory cytokines by producing IL-17A and thereby exacerbate renal pathology. Thus, our data show that pathogen-induced TRM17 cells have a previously unrecognized function in aggravating autoimmune disease.Copyright © 2020 American Association for the Advancement of Science. All rights reserved.
- Published
- 2020