PTEN drives Th17 cell differentiation by preventing IL-2 production

T helper 17 (Th17) cells are a CD4(+) T cell subset that produces IL-17A to mediate inflammation and autoimmunity. IL-2 inhibits Th17 cell differentiation. However, the mechanism by which IL-2 is suppressed during Th17 cell differentiation remains unclear. Here, we show that phosphatase and tensin h...

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Detalles Bibliográficos
Autores principales: Kim, Hyeong Su, Jang, Sung Woong, Lee, Wonyong, Kim, Kiwan, Sohn, Hyogon, Hwang, Soo Seok, Lee, Gap Ryol
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2017
Materias:
Research Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679178/
https://www.ncbi.nlm.nih.gov/pubmed/29018045
http://dx.doi.org/10.1084/jem.20170523
Descripción
Sumario:T helper 17 (Th17) cells are a CD4(+) T cell subset that produces IL-17A to mediate inflammation and autoimmunity. IL-2 inhibits Th17 cell differentiation. However, the mechanism by which IL-2 is suppressed during Th17 cell differentiation remains unclear. Here, we show that phosphatase and tensin homologue (PTEN) is a key factor that regulates Th17 cell differentiation by suppressing IL-2 production. Th17-specific Pten deletion (Pten(fl/fl)Il17a(cre)) impairs Th17 cell differentiation in vitro and ameliorated symptoms of experimental autoimmune encephalomyelitis (EAE), a model of Th17-mediated autoimmune disease. Mechanistically, Pten deficiency up-regulates IL-2 and phosphorylation of STAT5, but reduces STAT3 phosphorylation, thereby inhibiting Th17 cell differentiation. PTEN inhibitors block Th17 cell differentiation in vitro and in the EAE model. Thus, PTEN plays a key role in Th17 cell differentiation by blocking IL-2 expression.

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