Proceedings of the National Academy of Sciences · 2022 · 10 citations · 32 references
Life SciencesCell BiologyImmunologyInflammationSignal TransductionTranscriptional RegulationCytokine SignalingGastrointestinal InflammationImmune Cell SignalingInflammatory Bowel DiseaseInflammatory SignalingT Cell BiologyCell Type-specific Transcriptional RegulationCell-type Specific TranscriptionInflammatory Bowel Disease ImmunoregulationInflammatory Bowel Disease PathogenesisJak-stat Signaling PathwayStat3 SignalingT Helper 17 DifferentiationTh17 Cell Differentiation
Significance STAT3 (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.
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Transforming growth factor-β induces development of the TH17 lineage
Paul R. Mangan, Laurie E. Harrington, Darrell B. O’Quinn et al. · Nature · 2006 · 3K citations