Priming for T helper type 2 differentiation by interleukin 2-mediated induction of IL-4 receptor α chain expression

T-helper type 2 (T(H)2) cells are essential for humoral immunity and host defense. Interleukin (IL)-4 drives T(H)2 differentiation and IL-2 augments Il4 chromatin accessibility. Here we demonstrated that IL-2, by inducing STAT5 binding to the Il4ra locus, is essential for inducing and maintaining IL...

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Autores principales: Liao, Wei, Schones, Dustin E., Oh, Jangsuk, Cui, Yongzhi, Cui, Kairong, Tae-Young, Roh, Zhao, Keji, Leonard, Warren J.
Formato: Texto
Lenguaje:English
Publicado: 2008
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2762127/
https://www.ncbi.nlm.nih.gov/pubmed/18820682
http://dx.doi.org/10.1038/ni.1656
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author Liao, Wei
Schones, Dustin E.
Oh, Jangsuk
Cui, Yongzhi
Cui, Kairong
Tae-Young, Roh
Zhao, Keji
Leonard, Warren J.
author_facet Liao, Wei
Schones, Dustin E.
Oh, Jangsuk
Cui, Yongzhi
Cui, Kairong
Tae-Young, Roh
Zhao, Keji
Leonard, Warren J.
author_sort Liao, Wei
collection PubMed
description T-helper type 2 (T(H)2) cells are essential for humoral immunity and host defense. Interleukin (IL)-4 drives T(H)2 differentiation and IL-2 augments Il4 chromatin accessibility. Here we demonstrated that IL-2, by inducing STAT5 binding to the Il4ra locus, is essential for inducing and maintaining IL-4Rα expression. Although IL-4 induces IL-4Rα expression, T-cell receptor-induced IL-4Rα expression was normal in Il4(-/-) but profoundly diminished in Il2(-/-) cells. Remarkably, forced IL-4Rα expression rescued T(H)2 differentiation in Il2(-/-) cells. Moreover, genome-wide mapping by ChIP-Seq reveals broad interaction of STAT5A and STAT5B with genes associated with T(H)2 differentiation. These results reveal a previously unappreciated function for IL-2 in ‘priming’ T cells for T(H)2 differentiation and in maintaining expression of Il4ra and other genes in T(H)2-committed cells.
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spelling pubmed-27621272009-10-15 Priming for T helper type 2 differentiation by interleukin 2-mediated induction of IL-4 receptor α chain expression Liao, Wei Schones, Dustin E. Oh, Jangsuk Cui, Yongzhi Cui, Kairong Tae-Young, Roh Zhao, Keji Leonard, Warren J. Nat Immunol Article T-helper type 2 (T(H)2) cells are essential for humoral immunity and host defense. Interleukin (IL)-4 drives T(H)2 differentiation and IL-2 augments Il4 chromatin accessibility. Here we demonstrated that IL-2, by inducing STAT5 binding to the Il4ra locus, is essential for inducing and maintaining IL-4Rα expression. Although IL-4 induces IL-4Rα expression, T-cell receptor-induced IL-4Rα expression was normal in Il4(-/-) but profoundly diminished in Il2(-/-) cells. Remarkably, forced IL-4Rα expression rescued T(H)2 differentiation in Il2(-/-) cells. Moreover, genome-wide mapping by ChIP-Seq reveals broad interaction of STAT5A and STAT5B with genes associated with T(H)2 differentiation. These results reveal a previously unappreciated function for IL-2 in ‘priming’ T cells for T(H)2 differentiation and in maintaining expression of Il4ra and other genes in T(H)2-committed cells. 2008-09-28 2008-11 /pmc/articles/PMC2762127/ /pubmed/18820682 http://dx.doi.org/10.1038/ni.1656 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Liao, Wei
Schones, Dustin E.
Oh, Jangsuk
Cui, Yongzhi
Cui, Kairong
Tae-Young, Roh
Zhao, Keji
Leonard, Warren J.
Priming for T helper type 2 differentiation by interleukin 2-mediated induction of IL-4 receptor α chain expression
title Priming for T helper type 2 differentiation by interleukin 2-mediated induction of IL-4 receptor α chain expression
title_full Priming for T helper type 2 differentiation by interleukin 2-mediated induction of IL-4 receptor α chain expression
title_fullStr Priming for T helper type 2 differentiation by interleukin 2-mediated induction of IL-4 receptor α chain expression
title_full_unstemmed Priming for T helper type 2 differentiation by interleukin 2-mediated induction of IL-4 receptor α chain expression
title_short Priming for T helper type 2 differentiation by interleukin 2-mediated induction of IL-4 receptor α chain expression
title_sort priming for t helper type 2 differentiation by interleukin 2-mediated induction of il-4 receptor α chain expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2762127/
https://www.ncbi.nlm.nih.gov/pubmed/18820682
http://dx.doi.org/10.1038/ni.1656
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