TY - JOUR
T1 - STAT3 regulates cytokine-mediated generation of inflammatory helper T cells
AU - Yang, Xuexian O.
AU - Panopoulos, Athanasia D.
AU - Nurieva, Roza
AU - Seon, Hee Chang
AU - Wang, Demin
AU - Watowich, Stephanie S.
AU - Dong, Chen
PY - 2007/3/30
Y1 - 2007/3/30
N2 - Interleukin-17 (IL-17)-producing helper T (TH) cells, named as TH IL-17, TH17, or inflammatory TH (THi), have been recently identified as a novel effector lineage. However, how cytokine signals mediate THi differentiation is unclear. We found that IL-6 functioned to up-regulate IL-23R and that IL-23 synergized with IL-6 in promoting THi generation. STAT3, activated by both IL-6 and IL-23, plays a critical role in THi development. A hyperactive form of STAT3 promoted THi development, whereas this differentiation process was greatly impaired in STAT3-deficient T cells. Moreover, STAT3 regulated the expression of retinoic acid receptor-related orphan receptor γ-T (RORγt), a THi-specific transcriptional regulator; STAT3 deficiency impaired RORγt expression and led to elevated expression of T-box expressed in T cells (T-bet) and Forkhead box P3 (Foxp3). Our data thus demonstrate a pathway whereby cytokines regulate THi differentiation through a selective STAT transcription factor that functions to regulate lineage-specific gene expression.
AB - Interleukin-17 (IL-17)-producing helper T (TH) cells, named as TH IL-17, TH17, or inflammatory TH (THi), have been recently identified as a novel effector lineage. However, how cytokine signals mediate THi differentiation is unclear. We found that IL-6 functioned to up-regulate IL-23R and that IL-23 synergized with IL-6 in promoting THi generation. STAT3, activated by both IL-6 and IL-23, plays a critical role in THi development. A hyperactive form of STAT3 promoted THi development, whereas this differentiation process was greatly impaired in STAT3-deficient T cells. Moreover, STAT3 regulated the expression of retinoic acid receptor-related orphan receptor γ-T (RORγt), a THi-specific transcriptional regulator; STAT3 deficiency impaired RORγt expression and led to elevated expression of T-box expressed in T cells (T-bet) and Forkhead box P3 (Foxp3). Our data thus demonstrate a pathway whereby cytokines regulate THi differentiation through a selective STAT transcription factor that functions to regulate lineage-specific gene expression.
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U2 - 10.1074/jbc.C600321200
DO - 10.1074/jbc.C600321200
M3 - Article
C2 - 17277312
AN - SCOPUS:34247593586
SN - 0021-9258
VL - 282
SP - 9358
EP - 9363
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 13
ER -