TY - JOUR
T1 - IL-9 induces differentiation of TH17 cells and enhances function of FoxP3+ natural regulatory T cells
AU - Elyaman, Wassim
AU - Bradshaw, Elizabeth M.
AU - Uyttenhove, Catherine
AU - Dardalhon, Valérie
AU - Awasthi, Amit
AU - Imitola, Jaime
AU - Bettelli, Estelle
AU - Oukka, Mohamed
AU - Van Snick, Jacques
AU - Renauld, Jean Christophe
AU - Kuchroo, Vijay K.
AU - Khoury, Samia J.
PY - 2009/8/4
Y1 - 2009/8/4
N2 - 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.
AB - 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.
KW - Autoimmunity
KW - Regulatory cells
KW - Tolerance
UR - http://www.scopus.com/inward/record.url?scp=69149107148&partnerID=8YFLogxK
U2 - 10.1073/pnas.0812530106
DO - 10.1073/pnas.0812530106
M3 - Article
C2 - 19433802
AN - SCOPUS:69149107148
SN - 0027-8424
VL - 106
SP - 12885
EP - 12890
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 31
ER -