title: Interferon-regulatory factor 4 is essential for the developmental program of T helper 9 cells.
abstract: 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.
authors.affiliation: Institute for Immunology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.
authors.forename: Valérie
authors.initials: V
authors.lastname: Staudt
authors.forename: Evita
authors.initials: E
authors.lastname: Bothur
authors.forename: Matthias
authors.initials: M
authors.lastname: Klein
authors.forename: Karen
authors.initials: K
authors.lastname: Lingnau
authors.forename: Sebastian
authors.initials: S
authors.lastname: Reuter
authors.forename: Nadine
authors.initials: N
authors.lastname: Grebe
authors.forename: Bastian
authors.initials: B
authors.lastname: Gerlitzki
authors.forename: Markus
authors.initials: M
authors.lastname: Hoffmann
authors.forename: Alexander
authors.initials: A
authors.lastname: Ulges
authors.forename: Christian
authors.initials: C
authors.lastname: Taube
authors.forename: Nina
authors.initials: N
authors.lastname: Dehzad
authors.forename: Marc
authors.initials: M
authors.lastname: Becker
authors.forename: Michael
authors.initials: M
authors.lastname: Stassen
authors.forename: Andrea
authors.initials: A
authors.lastname: Steinborn
authors.forename: Michael
authors.initials: M
authors.lastname: Lohoff
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Schild
authors.forename: Edgar
authors.initials: E
authors.lastname: Schmitt
authors.forename: Tobias
authors.initials: T
authors.lastname: Bopp
mesh_terms: D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D050835:Interferon Regulatory Factors / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016906:Interleukin-9 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*; D000099218:Interferon Regulatory Factor-4
chemical_list: D050835:Interferon Regulatory Factors; D016906:Interleukin-9; D034741:RNA, Small Interfering; D000099218:Interferon Regulatory Factor-4