西亚试剂：Interferon-Regulatory Factor 4 Is Essential for the Develop

Interferon-Regulatory Factor 4 Is Essential for the Developmental Program of T Helper 9 Cells

Valérie Staudt1, 6, Evita Bothur3, 6, Matthias Klein1, Karen Lingnau4, Sebastian Reuter2, Nadine Grebe1, Bastian Gerlitzki1, Markus Hoffmann1, Alexander Ulges1, Christian Taube2, Nina Dehzad2, Marc Becker1, Michael Stassen1, Andrea Steinborn5, Michael Lohoff3, Hansj?rg Schild1, Edgar Schmitt1, 7 and Tobias Bopp1

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  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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