title: Bach2-Batf interactions control Th2-type immune response by regulating the IL-4 amplification loop.
abstract: Although Bach2 has an important role in regulating the Th2-type immune response, the underlying molecular mechanisms remain unclear. We herein demonstrate that Bach2 associates with Batf and binds to the regulatory regions of the Th2 cytokine gene loci. The Bach2-Batf complex antagonizes the recruitment of the Batf-Irf4 complex to AP-1 motifs and suppresses Th2 cytokine production. Furthermore, we find that Bach2 regulates the Batf and Batf3 expressions via two distinct pathways. First, Bach2 suppresses the maintenance of the Batf and Batf3 expression through the inhibition of IL-4 production. Second, the Bach2-Batf complex directly binds to the Batf and Batf3 gene loci and reduces transcription by interfering with the Batf-Irf4 complex. These findings suggest that IL-4 and Batf form a positive feedback amplification loop to induce Th2 cell differentiation and the subsequent Th2-type immune response, and Bach2-Batf interactions are required to prevent an excessive Th2 response.
authors: Department of Immunology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan.|Department of Translational Immunology, Translational Research Center, Ehime University Hospital, Shitsukawa, Toon, Ehime 791-0295, Japan.|Division of Immune Regulation, Department of Proteo-Inovation, Proteo-Science Center, Ehime University, Toon, Ehime 791-0295, Japan.
authors: Makoto
authors: M
authors: Kuwahara
authors: Department of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors: Wataru
authors: W
authors: Ise
authors: Department of Immunology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan.|Division of Cell-Free Sciences, Department of Proteo-Research, Proteo-Science Center, Ehime University, Matsuyama, Ehime 790-8577, Japan.
authors: Mizuki
authors: M
authors: Ochi
authors: Department of Translational Immunology, Translational Research Center, Ehime University Hospital, Shitsukawa, Toon, Ehime 791-0295, Japan.|Department of Hematology, Clinical Immunology and Infectious Diseases, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan.
authors: Junpei
authors: J
authors: Suzuki
authors: Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, 1-7-22 suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
authors: Kohei
authors: K
authors: Kometani
authors: Department of Immunology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan.
authors: Saho
authors: S
authors: Maruyama
authors: Department of Immunology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan.
authors: Maya
authors: M
authors: Izumoto
authors: Department of Infection and Host Defenses, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan.
authors: Akira
authors: A
authors: Matsumoto
authors: Division of Proteomics, Department of Proteo-Medicine, Proteo-Science Center, Ehime University, Toon, Ehime 791-0295, Japan.
authors: Nobuaki
authors: N
authors: Takemori
authors: Division of Proteomics, Department of Proteo-Medicine, Proteo-Science Center, Ehime University, Toon, Ehime 791-0295, Japan.
authors: Ayako
authors: A
authors: Takemori
authors: Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 Japan.
authors: Kenta
authors: K
authors: Shinoda
authors: Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 Japan.
authors: Toshinori
authors: T
authors: Nakayama
authors: Human DNA Analysis Group, Department of Technology Development, Kazusa DNA Research Institute, 2-6-7 Kazusa-Kamatari, Kisarazu, Chiba 292-0818, Japan.
authors: Osamu
authors: http://orcid.org/0000-0002-3328-9571
authors: O
authors: Ohara
authors: Department of Hematology, Clinical Immunology and Infectious Diseases, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan.
authors: Masaki
authors: M
authors: Yasukawa
authors: Division of Cell-Free Sciences, Department of Proteo-Research, Proteo-Science Center, Ehime University, Matsuyama, Ehime 790-8577, Japan.
authors: Tatsuya
authors: T
authors: Sawasaki
authors: Department of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.|Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, 1-7-22 suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
authors: Tomohiro
authors: T
authors: Kurosaki
authors: Department of Immunology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan.|Department of Translational Immunology, Translational Research Center, Ehime University Hospital, Shitsukawa, Toon, Ehime 791-0295, Japan.|Division of Immune Regulation, Department of Proteo-Inovation, Proteo-Science Center, Ehime University, Toon, Ehime 791-0295, Japan.
authors: Masakatsu
authors: M
authors: Yamashita
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D050835:Interferon Regulatory Factors / Q000235:genetics* / Q000378:metabolism; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology*; D014158:Transcription, Genetic / Q000235:genetics; D000099218:Interferon Regulatory Factor-4
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D050835:Interferon Regulatory Factors; D015847:Interleukin-4; D012097:Repressor Proteins; D050800:STAT6 Transcription Factor; D000099218:Interferon Regulatory Factor-4; C102109:Bach2 protein, mouse; C431772:Batf protein, mouse; C533289:SNFT protein, mouse; C494100:Stat6 protein, mouse