Open AccessIL-9 induces differentiation of T H 17 cells and enhances function of FoxP3 + natural regulatory T cells
Author(s) -
Wassim Elyaman,
Elizabeth M. Bradshaw,
Catherine Uyttenhove,
Valérie Dardalhon,
Amit Awasthi,
Jaime Imitola,
Estelle Bettelli,
Mohamed Oukka,
Jacques Van Snick,
JeanChristophe Renauld,
Vijay K. Kuchroo,
Samia J. Khoury
Publication year - 2009
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0812530106
Subject(s) - foxp3 , interleukin 21 , microbiology and biotechnology , zap70 , interleukin 3 , natural killer t cell , il 2 receptor , biology , t cell , cytotoxic t cell , immune system , stat5 , chemistry , signal transduction , in vitro , immunology , biochemistry
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.