title: BATF2 inhibits immunopathological Th17 responses by suppressingIl23aexpression duringTrypanosoma cruziinfection.
abstract: Inappropriate IL-17 responses are implicated in chronic tissue inflammation. IL-23 contributes toTrypanosoma cruzi-specific IL-17 production, but the molecular mechanisms underlying regulation of the IL-23-IL-17 axis duringT. cruziinfection are poorly understood. Here, we demonstrate a novel function of BATF2 as a negative regulator ofIl23ain innate immune cells. IL-17, but not IFN-γ, was more highly produced by CD4+T cells from spleens and livers ofT. cruzi-infectedBatf2-/-mice than by those of wild-type mice. In this context,Batf2-/-mice showed severe multiorgan pathology despite reduced parasite burden.T. cruzi-induced IL-23 production was increased inBatf2-/-innate immune cells. TheT. cruzi-induced enhanced Th17 response was abrogated inBatf2-/-Il23a-/-mice. The interaction of BATF2 with c-JUN prevented c-JUN-ATF-2 complex formation, inhibitingIl23aexpression. These results demonstrate that IFN-γ-inducible BATF2 in innate immune cells controls Th17-mediated immunopathology by suppressing IL-23 production duringT. cruziinfection.
authors.affiliation: Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.|WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.|Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Kitada
authors.affiliation: Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.|WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.|Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan.
authors.forename: Hisako
authors.identifier: 0000-0001-5676-8228
authors.initials: H
authors.lastname: Kayama
authors.affiliation: DNA-Chip Developmental Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Daisuke
authors.identifier: 0000-0002-4552-783X
authors.initials: D
authors.lastname: Okuzaki
authors.affiliation: Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Koga
authors.affiliation: Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Division of Molecular Neuroimmunology, Institute for Genetic Medicine, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan.
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Arima
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kumanogoh
authors.affiliation: Division of Molecular Neuroimmunology, Institute for Genetic Medicine, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Murakami
authors.affiliation: Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Masahito
authors.identifier: 0000-0001-9859-6217
authors.initials: M
authors.lastname: Ikawa
authors.affiliation: Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan ktakeda@ongene.med.osaka-u.ac.jp.|WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.|Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan.
authors.forename: Kiyoshi
authors.identifier: 0000-0002-1778-6332
authors.initials: K
authors.lastname: Takeda
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000502:physiology*; D014355:Chagas Disease / Q000276:immunology* / Q000473:pathology; D005260:Female; D007113:Immunity, Innate / Q000276:immunology; D053760:Interleukin-23 Subunit p19 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology; D058504:Th17 Cells / Q000276:immunology / Q000502:physiology*; D014349:Trypanosoma cruzi / Q000276:immunology*
chemical_list: C576672:BATF2 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; C508841:Il23a protein, mouse; D053760:Interleukin-23 Subunit p19; D016755:Proto-Oncogene Proteins c-jun