Abstract
SignificanceSTAT3 (signal transducer and activator of transcription 3) is a master transcription factor that organizes cellular responses to cytokines and growth factors and is implicated in inflammatory disorders. STAT3 is a well-recognized therapeutic target for human cancer and inflammatory disorders, but how its function is regulated in a cell type-specific manner has been a major outstanding question. We discovered that Stat3 imposes self-directed regulation through controlling transcription of its own regulator homeodomain-interacting protein kinase 2 (Hipk2) in a T helper 17 (Th17) cell-specific manner. Our validation of the functional importance of the Stat3-Hipk2 axis in Th17 cell development in the pathogenesis of T cell-induced colitis in mice suggests an approach to therapeutically treat inflammatory bowel diseases that currently lack a safe and effective therapy.
Original language | English |
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Pages (from-to) | e2117112119 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 119 |
Issue number | 14 |
DOIs | |
State | Published - 5 Apr 2022 |
Keywords
- STAT3
- Th17 cell differentiation
- chromatin biology
- gene transcription