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Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12885-90. doi: 10.1073/pnas.0812530106. Epub 2009 May 11.

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

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  • 1Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Abstract

The development of T helper (T(H))17 and regulatory T (T(reg)) cells is reciprocally regulated by cytokines. Transforming growth factor (TGF)-beta alone induces FoxP3(+) T(reg) cells, but together with IL-6 or IL-21 induces T(H)17 cells. Here we demonstrate that IL-9 is a key molecule that affects differentiation of T(H)17 cells and T(reg) function. IL-9 predominantly produced by T(H)17 cells, synergizes with TGF-beta1 to differentiate naïve CD4(+) T cells into T(H)17 cells, while IL-9 secretion by T(H)17 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 nT(regs) in vivo, leading to an increase in effector cells and worsening of experimental autoimmune encephalomyelitis. The mechanism of IL-9 effects on T(H)17 and T(regs) 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.

PMID:
19433802
[PubMed - indexed for MEDLINE]
PMCID:
PMC2722314
Free PMC Article
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