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

被引：153
作者：
Kashiwagi, Ikkou [1 ,2 ]
Morita, Rimpei [1 ,2 ]
Schichita, Takashi [1 ,2 ,3 ]
Komai, Kyoko [1 ,2 ]
Saeki, Keita [1 ,2 ]
Matsumoto, Makoto [4 ]
Takeda, Kiyoshi [5 ]
Nomura, Masatoshi [6 ]
Hayashi, Atsushi [2 ,7 ,8 ]
Kanai, Takanori [2 ,7 ]
Yoshimura, Akihiko [1 ,2 ]
机构：
[1] Keio Univ, Sch Med, Dept Internal Med, Dept Microbiol & Immunol, Tokyo 1608582, Japan
[2] Japan Sci & Technol Agcy, CREST, Tokyo 1020076, Japan
[3] PRESTO Precursory Res Embryon Sci & Technol, Chiyoda Ku, Tokyo 1020075, Japan
[4] Hyogo Coll Med, Dept Immunol & Med Zool, Nishinomiya, Hyogo 6638501, Japan
[5] Osaka Univ, Dept Microbiol & Immunol, Grad Sch Med, WPI Immunol Frontier Res Ctr,Lab Immune Regulat, Suita, Osaka 5650871, Japan
[6] Kyushu Univ, Grad Sch Med Sci, Fukuoka 8128582, Japan
[7] Keio Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, Tokyo 1608582, Japan
[8] Miyarisan Pharmaceut Co Ltd, Res Lab, Tokyo 1140016, Japan
来源：
IMMUNITY | 2015年 / 43卷 / 01期
关键词：
GROWTH-FACTOR-BETA; T-CELLS; COMMENSAL; TRANSCRIPTION; SUPPRESSION; INDUCTION; DIFFERENTIATION; COACTIVATORS; MACROPHAGES; DISRUPTION;
D O I：
10.1016/j.immuni.2015.06.010
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Colonizationwith a mixture of Clostridium species has been shown to induce accumulation of induced regulatory T (iTreg) cells in the colon. Transforming growth factor-beta (TGF-beta) is an essential factor for iTreg cell induction; however, the relationship between Clostridium species and TGF-beta 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-beta 1 from lamina propria dendritic cells (LPDCs). C. butyricum-mediated TGF-beta 1 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-beta-Smad3 transcription factor signal was necessary for robust TGF-beta expression in DCs, whereas Smad2 negatively regulated TGF-beta expression. Smad2-deficient DCs expressed higher concentrations of TGF-beta and were tolerogenic for colitismodels. This study reveals a novel mechanism of TGF-beta induction by Clostridia through a cooperation between TLR2-AP-1 and TGF-beta-Smad signaling pathways.
引用
收藏
页码：65 / 79
页数：15
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