Year: 2021
Type: preprint
Abstract: Summary The cytokine receptor IL-23R plays a fundamental role in inflammation and autoimmunity. However, several observations have been difficult to reconcile under the assumption that only Th17 cells critically depend on IL-23 to acquire a pathogenic phenotype. Here, we report that Th1 cells differentiated in vitro with IL-12 + IL-21 show similar levels of IL-23R expression as in pathogenic Th17 cells. We demonstrate that IL-23R is required for Th1 cells to acquire a highly colitogenic phenotype. scRNAseq analysis of intestinal T cells enabled us to identify novel regulators induced by IL-23R-signaling in Th1 cells which differed from those expressed in Th17 cells. The perturbation of one of these regulators (CD160) in Th1 cells inhibited induction of colitis. In this process, we were able to uncouple IL-23R as a purely Th17 cell-specific factor and implicate IL-23R signaling as a pathogenic driver of Th1 cell-mediated tissue inflammation and disease.
Institutions: Broad Institute, Brigham and Women's Hospital, Harvard University, Klarman Cell Observatory, University of California, Berkeley, Howard Hughes Medical Institute, Massachusetts General Hospital, Ragon Institute of MGH, MIT and Harvard, Chan Zuckerberg Biohub San Francisco, Massachusetts Institute of Technology
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funder: Multiple Sclerosis Society
OpenAlex ID: W3122723243