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Updated: Jun 14, 2026

Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes
Published on: September 26, 2013
Interleukin 23 promotes a pro-inflammatory Th17 cell state by stabilizing RORγt and suppressing glucocorticoid
Dandan Yang1, Linglin Huang1, Jianfei Yang2
1Gene Lay Institute of Immunology and Inflammation, Harvard Medical School and Mass General Brigham, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02149, USA; Ann Romney Center for Neurologic Diseases, Harvard Medical School and Mass General Brigham, Boston, MA 02115, USA.
None:
Interleukin 23 receptor (IL-23R) signaling is critical for the generation of pro-inflammatory CD4+ 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.
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