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Smad2 and Smad3 Inversely Regulate TGF-ß Autoinduction in Clostridium butyricum-Activated Dendritic Cells.
Kashiwagi, Ikkou; Morita, Rimpei; Schichita, Takashi; Komai, Kyoko; Saeki, Keita; Matsumoto, Makoto; Takeda, Kiyoshi; Nomura, Masatoshi; Hayashi, Atsushi; Kanai, Takanori; Yoshimura, Akihiko.
Affiliation
  • Kashiwagi I; Department of Microbiology and Immunology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan, and Japan Science and Technology Agency, CREST, Tokyo 102-0076, Japan.
  • Morita R; Department of Microbiology and Immunology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan, and Japan Science and Technology Agency, CREST, Tokyo 102-0076, Japan.
  • Schichita T; Department of Microbiology and Immunology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan, and Japan Science and Technology Agency, CREST, Tokyo 102-0076, Japan; PRESTO (Precursory Research for Embryonic Science and Technology), Chiyoda-ku, Tokyo 102-0075,
  • Komai K; Department of Microbiology and Immunology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan, and Japan Science and Technology Agency, CREST, Tokyo 102-0076, Japan.
  • Saeki K; Department of Microbiology and Immunology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan, and Japan Science and Technology Agency, CREST, Tokyo 102-0076, Japan.
  • Matsumoto M; Department of Immunology and Medical Zoology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan.
  • Takeda K; Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
  • Nomura M; Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
  • Hayashi A; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan, and Japan Science and Technology Agency, CREST, Tokyo 102-0076, Japan; Miyarisan Pharmaceutical Co., Ltd., Research Laboratory, Tokyo 114-0016, Japan.
  • Kanai T; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan, and Japan Science and Technology Agency, CREST, Tokyo 102-0076, Japan.
  • Yoshimura A; Department of Microbiology and Immunology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan, and Japan Science and Technology Agency, CREST, Tokyo 102-0076, Japan. Electronic address: yoshimura@a6.keio.jp.
Immunity ; 43(1): 65-79, 2015 Jul 21.
Article in En | MEDLINE | ID: mdl-26141582
ABSTRACT
Colonization with a mixture of Clostridium species has been shown to induce accumulation of induced regulatory T (iTreg) cells in the colon. Transforming growth factor-ß (TGF-ß) is an essential factor for iTreg cell induction; however, the relationship between Clostridium species and TGF-ß remains to be clarified. Here we demonstrated that a gram-positive probiotic bacterial strain, Clostridium butyricum (C. butyricum), promoted iTreg cell generation in the intestine through induction of TGF-ß1 from lamina propria dendritic cells (LPDCs). C. butyricum-mediated TGF-ß1 induction was mainly Toll-like receptor 2 (TLR2) dependent, and the ERK-AP-1 kinase pathway played an important role. In addition, the autocrine TGF-ß-Smad3 transcription factor signal was necessary for robust TGF-ß expression in DCs, whereas Smad2 negatively regulated TGF-ß expression. Smad2-deficient DCs expressed higher concentrations of TGF-ß and were tolerogenic for colitis models. This study reveals a novel mechanism of TGF-ß induction by Clostridia through a cooperation between TLR2-AP-1 and TGF-ß-Smad signaling pathways.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Dendritic Cells / Clostridium butyricum / Smad2 Protein / Smad3 Protein / Transforming Growth Factor beta1 Type of study: Prognostic_studies Limits: Animals Language: En Journal: Immunity Journal subject: ALERGIA E IMUNOLOGIA Year: 2015 Type: Article Affiliation country: Japan
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Dendritic Cells / Clostridium butyricum / Smad2 Protein / Smad3 Protein / Transforming Growth Factor beta1 Type of study: Prognostic_studies Limits: Animals Language: En Journal: Immunity Journal subject: ALERGIA E IMUNOLOGIA Year: 2015 Type: Article Affiliation country: Japan