Interleukin 23 promotes a pro-inflammatory Th17 cell state by stabilizing RORγt and suppressing glucocorticoid receptor activity
Year: 2026
Type: article
Abstract: IL-17-producing T helper cells (Th17) that can drive autoimmune tissue inflammation, but the underlying mechanisms are not clear. We integrated phosphoproteomic and transcriptomic data downstream of IL-23R and IL-12 receptor (IL-12R), which share a common subunit, to identify mechanisms engaged specifically by IL-23. We identified chromodomain helicase DNA-binding protein 1 (CHD1), an epigenetic regulator, and the glucocorticoid receptor (GR), a transcription factor (TF), as mediators of IL-23R signaling. IL-23R activation promoted CHD1 interaction with TF STAT3 and co-binding at the TF RORγt locus to enforce a pro-inflammatory Th17 state. Conversely, IL-23R signaling altered phosphorylation of the GR, thereby preventing its activation and nuclear translocation, ultimately impairing GR-driven inhibition of pro-inflammatory Th17 gene programs. Our findings uncover two mechanisms by which IL-23 promotes a pro-inflammatory Th17 cell state, offering potential therapeutic targets for treating Th17-driven autoimmune tissue inflammation and restoring homeostasis.
Source: Immunity
Authors: Dandan Yang, Linglin Huang, Jianfei Yang, Oier Etxezarreta-Arrastoa, Markus A. Schramm, Alex V. Khodaverdian, Nandini Acharya, Sai Harsha Krovi, Karen Dixon, Hanning Cheng, Katherine L. Wei, Junrong Xia, Fan Cheng, Alissa J. Nelson, Kathryn Abell, Jian Min Ren, Vicky Yang, Timothy Sikorski, Roland Annan, Stephanie Van Horn, Christopher Traini, Thad Carlson, Rajesh K. Krishnan, Matthew P. Stokes, Raymond A. Sobel, Nir Yosef, Ana C. Anderson, Vijay K. Kuchroo
Institutions: Broad Institute, Harvard University, Mass General Brigham, Weizmann Institute of Science, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Wexner Medical Center, The Ohio State University, Massachusetts Institute of Technology, Cell Signaling Technology (United States), GlaxoSmithKline (United States), Stanford Medicine, Stanford University
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
OpenAlex ID: W7164571079