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 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.
Moisan
Jacques
J
Rheumatology, Immunology and Allergy, Brigham and Women's Hospital/Harvard Medical School, Boston, MA 02115, USA.
Grenningloh
Roland
R
Bettelli
Estelle
E
Oukka
Mohamed
M
Ho
I-Cheng
IC
D000818:Animals; D002454:Cell Differentiation; D005091:Exons; D020381:Interleukin-17 / Q000235:genetics; D015759:Ionomycin / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D050784:Proto-Oncogene Protein c-ets-1 / Q000172:deficiency / Q000235:genetics*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
C494042:Ets1 protein, mouse; D020381:Interleukin-17; D050784:Proto-Oncogene Protein c-ets-1; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate