IL-9 induces differentiation of TH17 cells and enhances function of FoxP3+ natural regulatory T cells

Wassim Elyaman, Elizabeth M. Bradshaw, Catherine Uyttenhove, Valérie Dardalhon, Amit Awasthi, Jaime Imitola, Estelle Bettelli, Mohamed Oukka, Jacques Van Snick, Jean Christophe Renauld, Vijay K. Kuchroo, Samia J. Khoury

Research output: Contribution to journalArticlepeer-review

372 Scopus citations


The development of T helper (TH)17 and regulatory T (T reg) cells is reciprocally regulated by cytokines. Transforming growth factor (TGF)-β alone induces FoxP3+ Treg cells, but together with IL-6 or IL-21 induces TH17 cells. Here we demonstrate that IL-9 is a key molecule that affects differentiation of T H17 cells and Treg function. IL-9 predominantly produced by TH17 cells, synergizes with TGF-β1 to differentiate naïve CD4+ T cells into TH17 cells, while IL-9 secretion by TH17 cells is regulated by IL-23. Interestingly, IL-9 enhances the suppressive functions of FoxP3+ CD4+ T reg cells in vitro, and absence of IL-9 signaling weakens the suppressive activity of nTregs in vivo, leading to an increase in effector cells and worsening of experimental autoimmune encephalomyelitis. The mechanism of IL-9 effects on TH17 and Tregs is through activation of STAT3 and STAT5 signaling. Our findings highlight a role of IL-9 as a regulator of pathogenic versus protective mechanisms of immune responses.

Original languageEnglish
Pages (from-to)12885-12890
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number31
StatePublished - Aug 4 2009
Externally publishedYes


  • Autoimmunity
  • Regulatory cells
  • Tolerance


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