STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J Biol Chem 2007 Mar 30;282(13):9358-9363
Date
02/06/2007Pubmed ID
17277312DOI
10.1074/jbc.C600321200Scopus ID
2-s2.0-34247593586 (requires institutional sign-in at Scopus site) 1253 CitationsAbstract
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.
Author List
Yang XO, Panopoulos AD, Nurieva R, Chang SH, Wang D, Watowich SS, Dong CAuthor
Demin Wang PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Differentiation
Inflammation
Interferon-gamma
Interleukin-6
Mice
Mice, Inbred C57BL
Mice, Knockout
STAT3 Transcription Factor
T-Lymphocytes, Helper-Inducer