Induction of a colitogenic phenotype in Th1 cells depends on IL-23R signaling
Induction of a colitogenic phenotype in Th1 cells depends on IL-23R signaling
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.
Xavier Ramnik J.、Pawlak Mathias、DeTomaso David、zu Horste Gerd Meyer、Lee Youjin、Nyman Jackson、Dionne Danielle、Wang Chao、Burkett Patrick R.、Kuchroo Vijay K.、Regev Aviv、Anderson Ana C.、Wallrapp Antonia、Yosef Nir、Riesenfeld Samantha J.
Klarman Cell Observatory, Broad Institute of MIT and Harvard||Department of Molecular BiologyEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women?ˉs Hospital||Klarman Cell Observatory, Broad Institute of MIT and HarvardDepartment of Electrical Engineering and Computer Science and Center for computational biologyEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women?ˉs HospitalEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women?ˉs HospitalKlarman Cell Observatory, Broad Institute of MIT and HarvardKlarman Cell Observatory, Broad Institute of MIT and HarvardEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women?ˉs Hospital||Klarman Cell Observatory, Broad Institute of MIT and HarvardEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women?ˉs Hospital||Klarman Cell Observatory, Broad Institute of MIT and HarvardEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women?ˉs Hospital||Klarman Cell Observatory, Broad Institute of MIT and HarvardKlarman Cell Observatory, Broad Institute of MIT and Harvard||Howard Hughes Medical InstituteEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women?ˉs Hospital||Klarman Cell Observatory, Broad Institute of MIT and HarvardEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women?ˉs Hospital||Klarman Cell Observatory, Broad Institute of MIT and HarvardDepartment of Electrical Engineering and Computer Science and Center for computational biology||Chan-Zuckerberg Biohub||Ragon Institute of MGHKlarman Cell Observatory, Broad Institute of MIT and Harvard
基础医学分子生物学
Xavier Ramnik J.,Pawlak Mathias,DeTomaso David,zu Horste Gerd Meyer,Lee Youjin,Nyman Jackson,Dionne Danielle,Wang Chao,Burkett Patrick R.,Kuchroo Vijay K.,Regev Aviv,Anderson Ana C.,Wallrapp Antonia,Yosef Nir,Riesenfeld Samantha J..Induction of a colitogenic phenotype in Th1 cells depends on IL-23R signaling[EB/OL].(2025-03-28)[2025-08-24].https://www.biorxiv.org/content/10.1101/2021.01.24.426445.点此复制
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