Interferon-regulatory factor 4 is essential for the developmental program of T helper 9 cells

Interferon-regulatory factor 4 (IRF4) is essential for the development of T helper 2 (Th2) and Th17 cells. Herein, we report that IRF4 is also crucial for the development and function of an interleukin-9 (IL-9)-producing CD4(+) T cell subset designated Th9. IRF4-deficient CD4(+) T cells failed to de...

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Main Authors: Staudt, Valérie (Author) , Bothur, Evita (Author) , Klein, Matthias (Author) , Lingnau, Karen (Author) , Reuter, Sebastian (Author) , Grebe, Nadine (Author) , Gerlitzki, Bastian (Author) , Hoffmann, Markus (Author) , Ulges, Alexander (Author) , Taube, Christian (Author) , Dehzad, Nina (Author) , Becker, Marc (Author) , Stassen, Michael (Author) , Steinborn-Kröhl, Andrea (Author) , Lohoff, Michael (Author) , Schild, Hansjörg (Author) , Schmitt, Edgar (Author) , Bopp, Tobias (Author)
Format: Article (Journal)
Language:English
Published: August 27, 2010
In: Immunity
Year: 2010, Volume: 33, Issue: 2, Pages: 192-202
ISSN:1097-4180
Online Access: Get full text
Author Notes:Valérie Staudt, Evita Bothur, Matthias Klein, Karen Lingnau, Sebastian Reuter, Nadine Grebe, Bastian Gerlitzki, Markus Hoffmann, Alexander Ulges, Christian Taube, Nina Dehzad, Marc Becker, Michael Stassen, Andrea Steinborn, Michael Lohoff, Hansjörg Schild, Edgar Schmitt, and Tobias Bopp

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520 |a Interferon-regulatory factor 4 (IRF4) is essential for the development of T helper 2 (Th2) and Th17 cells. Herein, we report that IRF4 is also crucial for the development and function of an interleukin-9 (IL-9)-producing CD4(+) T cell subset designated Th9. IRF4-deficient CD4(+) T cells failed to develop into IL-9-producing Th9 cells, and IRF4-specific siRNA inhibited IL-9 production in wild-type CD4(+) T cells. Chromatin-immunoprecipitation (ChIP) analyses revealed direct IRF4 binding to the Il9 promoter in Th9 cells. In a Th9-dependent asthma model, neutralization of IL-9 substantially ameliorated asthma symptoms. The relevance of these findings is emphasized by the fact that the induction of IL-9 production also occurs in human CD4(+) T cells accompanied by the upregulation of IRF4. Our data clearly demonstrate the central function of IRF4 in the development of Th9 cells and underline the contribution of this T helper cell subset to the pathogenesis of asthma. 
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