Ets-1 is a negative regulator of Th17 differentiation

IL-17 is a proinflammatory cytokine that plays a role in the clearance of extracellular bacteria and contributes to the pathology of many autoimmune and allergic conditions. IL-17 is produced mainly by a newly characterized subset of T helper (Th) cells termed Th17. Although the role of Th17 cells i...

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Published inThe Journal of experimental medicine Vol. 204; no. 12; pp. 2825 - 2835
Main Authors Moisan, Jacques, Grenningloh, Roland, Bettelli, Estelle, Oukka, Mohamed, Ho, I-Cheng
Format Journal Article
LanguageEnglish
Published United States The Rockefeller University Press 26.11.2007
Subjects
Animals
Cell Differentiation
Exons
Interleukin-17 - genetics
Ionomycin - pharmacology
Mice
Mice, Knockout
Proto-Oncogene Protein c-ets-1 - deficiency
Proto-Oncogene Protein c-ets-1 - genetics
T-Lymphocytes, Helper-Inducer - cytology
T-Lymphocytes, Helper-Inducer - drug effects
T-Lymphocytes, Helper-Inducer - immunology
Tetradecanoylphorbol Acetate - pharmacology
Th1 Cells - drug effects
Th1 Cells - immunology
Th2 Cells - drug effects
Th2 Cells - immunology
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Summary:IL-17 is a proinflammatory cytokine that plays a role in the clearance of extracellular bacteria and contributes to the pathology of many autoimmune and allergic conditions. IL-17 is produced mainly by a newly characterized subset of T helper (Th) cells termed Th17. Although the role of Th17 cells in the pathology of autoimmune diseases is well established, the transcription factors regulating the differentiation of Th17 cells remain poorly characterized. We report that Ets-1-deficient Th cells differentiated more efficiently to Th17 cells than wild-type cells. This was attributed to both low IL-2 production and increased resistance to the inhibitory effect of IL-2 on Th17 differentiation. The resistance to IL-2 suppression was caused by a defect downstream of STAT5 phosphorylation, but was not caused by a difference in the level of RORgamma t. Furthermore, Ets-1-deficient mice contained an abnormally high level of IL-17 transcripts in their lungs and exhibited increased mucus production by airway epithelial cells in an IL-17-dependent manner. Based on these observations, we report that Ets-1 is a negative regulator of Th17 differentiation.
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CORRESPONDENCE I-Cheng Ho: iho@partners.org
Abbreviations used: CHIP, chromatin immunoprecipitation; ICS, intracellular cytokine staining; PAS, periodic acid Schiff.
ISSN:0022-1007
1540-9538
1892-1007
DOI:10.1084/jem.20070994