Smad2 and Smad3 Inversely Regulate TGF-β Autoinduction in Clostridium butyricum-Activated Dendritic Cells

Ikkou Kashiwagi, Rimpei Morita, Takashi Schichita, Kyoko Komai, Keita Saeki, Makoto Matsumoto, Kiyoshi Takeda, Masatoshi Nomura, Atsushi Hayashi, Takanori Kanai, Akihiko Yoshimura

Research output: Contribution to journalArticle

79 Citations (Scopus)

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-β (TGF-β) is an essential factor for iTreg cell induction; however, the relationship between Clostridium species and TGF-β 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-β1 from lamina propria dendritic cells (LPDCs). C. butyricum-mediated TGF-β1 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-β-Smad3 transcription factor signal was necessary for robust TGF-β expression in DCs, whereas Smad2 negatively regulated TGF-β expression. Smad2-deficient DCs expressed higher concentrations of TGF-β and were tolerogenic for colitis models. This study reveals a novel mechanism of TGF-β induction by Clostridia through a cooperation between TLR2-AP-1 and TGF-β-Smad signaling pathways.

Original languageEnglish
Pages (from-to)65-79
Number of pages15
JournalImmunity
Volume43
Issue number1
DOIs
Publication statusPublished - 2015 Jul 21

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Smad2 and Smad3 Inversely Regulate TGF-β Autoinduction in Clostridium butyricum-Activated Dendritic Cells'. Together they form a unique fingerprint.

  • Cite this

    Kashiwagi, I., Morita, R., Schichita, T., Komai, K., Saeki, K., Matsumoto, M., Takeda, K., Nomura, M., Hayashi, A., Kanai, T., & Yoshimura, A. (2015). Smad2 and Smad3 Inversely Regulate TGF-β Autoinduction in Clostridium butyricum-Activated Dendritic Cells. Immunity, 43(1), 65-79. https://doi.org/10.1016/j.immuni.2015.06.010