STAT3 regulates cytokine-mediated generation of inflammatory helper T cells - PubMed (original) (raw)
. 2007 Mar 30;282(13):9358-9363.
doi: 10.1074/jbc.C600321200. Epub 2007 Feb 3.
Affiliations
- PMID: 17277312
- DOI: 10.1074/jbc.C600321200
Free article
STAT3 regulates cytokine-mediated generation of inflammatory helper T cells
Xuexian O Yang et al. J Biol Chem. 2007.
Free article
Abstract
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 gamma-T (RORgamma t), a THi-specific transcriptional regulator; STAT3 deficiency impaired RORgamma t 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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