Cheung, Ka LungJaganathan, AnbalaganHu, YuanXu, FeihongLejeune, AlannahSharma, RajalCaescu, Cristina I.Meslamani, JamelVincek, AdamZhang, FanLee, KyungZaware, NileshQayum, Amina AbdulRen, ChunyanKaplan, Mark H.He, John CijiangXiong, HuabaoZhou, Ming-Ming2023-08-282023-08-282022Cheung KL, Jaganathan A, Hu Y, et al. HIPK2 directs cell type-specific regulation of STAT3 transcriptional activity in Th17 cell differentiation. Proc Natl Acad Sci U S A. 2022;119(14):e2117112119. doi:10.1073/pnas.2117112119https://hdl.handle.net/1805/35168SignificanceSTAT3 (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.en-USAttribution-NonCommercial-NoDerivatives 4.0 InternationalGene transcriptionTh17 cell differentiationChromatin biologySTAT3Article