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

Christian F Krebs, Daniel Reimers, Yu Zhao, Hans-Joachim Paust, Patricia Bartsch, Sarah Nuñez, Mariana V Rosemblatt, Malte Hellmig, Christoph Kilian, Alina Borchers, Leon U B Enk, Michael Zinke, Martina Becker, Joanna Schmid, Stefanie Klinge, Milagros N Wong, Victor G Puelles, Constantin Schmidt, Tabea Bertram, Natascha Stumpf, Elion Hoxha, Catherine Meyer-Schwesinger, Maja T Lindenmeyer, Clemens D Cohen, Michael Rink, Christian Kurts, Sören Franzenburg, Friedrich Koch-Nolte, Jan-Eric Turner, Jan-Hendrik Riedel, Samuel Huber, Nicola Gagliani, Tobias B Huber, Thorsten Wiech, Holger Rohde, Maria Rosa Bono, Stefan Bonn, Ulf Panzer, Hans-Willi Mittrücker
Year of publication:
Journal title abbreviated:
Sci Immunol
Journal title long:
Science immunology
Impact factor:
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<sub>RM</sub>) cells persist in peripheral organs and provide immune protection against reinfection. However, whether T<sub>RM</sub> 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<sup>+</sup> T<sub>RM</sub> cells with a T<sub>H</sub>17 signature (termed T<sub>RM</sub>17 cells) in kidneys of patients with ANCA-associated glomerulonephritis. Experimental models demonstrated that renal T<sub>RM</sub>17 cells were induced by pathogens infecting the kidney, such as <i>Staphylococcus aureus</i>, <i>Candida albicans</i>, and uropathogenic <i>Escherichia coli</i>, and persisted after the clearance of infections. Upon induction of experimental glomerulonephritis, these kidney T<sub>RM</sub>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<sub>RM</sub>17 cells have a previously unrecognized function in aggravating autoimmune disease.