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

研究成果: Contribution to journalArticle査読

100 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)65-79
ページ数15
ジャーナルImmunity
43
1
DOI
出版ステータス出版済み - 7 21 2015

All Science Journal Classification (ASJC) codes

  • 免疫アレルギー学
  • 免疫学
  • 感染症

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