HIPK2 directs cell type-specific regulation of STAT3 transcriptional activity in Th17 cell differentiation

Ka Lung Cheung, Anbalagan Jaganathan, Yuan Hu, Feihong Xu, Alannah Lejeune, Rajal Sharma, Cristina I. Caescu, Jamel Meslamani, Adam Vincek, Fan Zhang, Kyung Lee, Nilesh Zaware, Amina Abdul Qayum, Chunyan Ren, Mark H. Kaplan, John Cijiang He, Huabao Xiong, Ming Ming Zhou

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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 languageEnglish
Pages (from-to)e2117112119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number14
DOIs
StatePublished - 5 Apr 2022

Keywords

  • STAT3
  • Th17 cell differentiation
  • chromatin biology
  • gene transcription

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