STAT6-dependent regulation of Th9 development

Ritobrata Goswami, Rukhsana Jabeen, Ryoji Yagi, Duy Pham, Jinfang Zhu, Shreevrat Goenka, Mark H. Kaplan

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Abstract

Th cell effector subsets develop in response to specific cytokine environments. The development of a particular cytokine-secreting pattern requires an integration of signals that may promote the development of opposing pathways. A recent example of this paradigm is the IL-9-secreting Th9 cell that develops in response to TGF-β and IL-4, cytokines that, in isolation, promote the development of inducible regulatory T cells and Th2 cells, respectively. To determine how the balance of these factors results in priming for IL-9 secretion, we examined the effects of each pathway on transcription factors that regulate Th cell differentiation. We demonstrated that TGF-β induces the PU.1-encoding Sfpi1 locus and that this is independent of IL-4-induced STAT6 activation. IL-4-activated STAT6 is required for repressing the expression of T-bet and Foxp3 in Th9 cells, transcription factors that inhibit IL-9 production, and STAT6 is required for the induction of IRF4, which promotes Th9 development. These data established a transcription factor network that regulates IL-9 and demonstrated how combinations of cytokine signals generate cytokine-secreting potential by altering the expression of a panel of transcription factors.

Original languageEnglish (US)
Pages (from-to)968-975
Number of pages8
JournalJournal of Immunology
Volume188
Issue number3
DOIs
StatePublished - Feb 1 2012

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Goswami, R., Jabeen, R., Yagi, R., Pham, D., Zhu, J., Goenka, S., & Kaplan, M. H. (2012). STAT6-dependent regulation of Th9 development. Journal of Immunology, 188(3), 968-975. https://doi.org/10.4049/jimmunol.1102840