Stat3 and Stat4 direct development of IL-17-secreting Th cells

Anubhav N. Mathur, Hua Chen Chang, Dimitrios G. Zisoulis, Gretta L. Stritesky, Qing Yu, John T. O'Malley, Reuben Kapur, David E. Levy, Geoffrey S. Kansas, Mark H. Kaplan

Research output: Contribution to journalArticle

409 Scopus citations

Abstract

IL-17-secreting CD4+ T cells are critically involved in inflammatory immune responses. Development of these cells is promoted in vivo and in vitro by IL-23 or TGFβ1 plus IL-6. Despite growing interest in this inflammatory Th subset, little is known about the transcription factors that are required for their development. We demonstrate that Stat3 is required for programming the TGFβ1 plus IL-6 and IL-23-stimulated IL-17-secreting phenotype, as well as for RORγt expression in TGFβ1 plus IL-6-primed cells. Moreover, retroviral transduction of a constitutively active Stat3 into differentiating T cell cultures enhances IL-17 production from these cells. We further show that Stat4 is partially required for the development of IL-23-, but not TGFβ1 plus IL-6-primed IL-17-secreting cells, and is absolutely required for IL-17 production in response to IL-23 plus IL-18. The requirements for Stat3 and Stat4 in the development of these IL-17-secreting subsets reveal additional mechanisms in Th cell fate decisions during the generation of proinflammatory cell types.

Original languageEnglish (US)
Pages (from-to)4901-4907
Number of pages7
JournalJournal of Immunology
Volume178
Issue number8
DOIs
StatePublished - Apr 15 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Mathur, A. N., Chang, H. C., Zisoulis, D. G., Stritesky, G. L., Yu, Q., O'Malley, J. T., Kapur, R., Levy, D. E., Kansas, G. S., & Kaplan, M. H. (2007). Stat3 and Stat4 direct development of IL-17-secreting Th cells. Journal of Immunology, 178(8), 4901-4907. https://doi.org/10.4049/jimmunol.178.8.4901