title: Arid5a regulates naive CD4+ T cell fate through selective stabilization of Stat3 mRNA.
abstract: Balance in signal transducer and activator of transcription (STAT) activation is a key factor in regulating the fate of naive CD4(+)T cells. Here, we demonstrate that AT-rich interactive domain-containing protein 5a (Arid5a) in T cells directs naive CD4(+)T cells to differentiate into inflammatory CD4(+)T cells, especially Th17 cells, through selective stabilization of Stat3(but not Stat1 and Stat5) mRNA in an IL-6-dependent manner. Loss of Arid5a in T cells led to reduction of STAT3 level under Th17-polarizing conditions, whereas STAT1 and STAT5 in Arid5a-deficient T cells were highly activated compared with those of WT T cells under the same conditions. These cells displayed the feature of antiinflammatory (Il10-expressing) CD4(+)T cells. Thus, we show a T cell-intrinsic role of Arid5a on fate decisions of naive CD4(+)T cells through selective stabilization of Stat3 mRNA.
authors.affiliation: Laboratory of Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan kazuya@ifrec.osaka-u.ac.jp kishimoto@ifrec.osaka-u.ac.jp.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Masuda
authors.affiliation: Laboratory of Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Barry
authors.initials: B
authors.lastname: Ripley
authors.affiliation: Laboratory of Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Kishan Kumar
authors.initials: KK
authors.lastname: Nyati
authors.affiliation: Laboratory of Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Praveen Kumar
authors.initials: PK
authors.lastname: Dubey
authors.affiliation: Laboratory of Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Mohammad Mahabub-Uz
authors.initials: MM
authors.lastname: Zaman
authors.affiliation: Biological Sciences Department, College of Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia.
authors.forename: Hamza
authors.initials: H
authors.lastname: Hanieh
authors.affiliation: Laboratory of Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Higa
authors.affiliation: Laboratory of System Immunology, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Laboratory of System Immunology, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Daron M
authors.initials: DM
authors.lastname: Standley
authors.affiliation: Structural Energy Bioscience Research Section, Institute of Advanced Energy, Kyoto University, Kyoto 611-0011, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Mashima
authors.affiliation: Structural Energy Bioscience Research Section, Institute of Advanced Energy, Kyoto University, Kyoto 611-0011, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Katahira
authors.affiliation: Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Okamoto
authors.affiliation: Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Matsuura
authors.affiliation: Laboratory of Infection and Prevention, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeuchi
authors.affiliation: Laboratory of Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan kazuya@ifrec.osaka-u.ac.jp kishimoto@ifrec.osaka-u.ac.jp.
authors.forename: Tadamitsu
authors.initials: T
authors.lastname: Kishimoto
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D020871:RNA Stability / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology*; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology*; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*
chemical_list: C582683:Arid5a protein, mouse; D004268:DNA-Binding Proteins; C556062:IL10 protein, mouse; D015850:Interleukin-6; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; D014157:Transcription Factors; D016753:Interleukin-10