Faculty Collaboration Database

STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J Biol Chem 2007 Mar 30;282(13):9358-63

Date

02/06/2007

Pubmed ID

17277312

DOI

10.1074/jbc.C600321200

Scopus ID

2-s2.0-34247593586   959 Citations

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.

Author List

Yang XO, Panopoulos AD, Nurieva R, Chang SH, Wang D, Watowich SS, Dong C

Author

Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cell Differentiation
Inflammation
Interferon-gamma
Interleukin-6
Mice
Mice, Inbred C57BL
Mice, Knockout
STAT3 Transcription Factor
T-Lymphocytes, Helper-Inducer