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

被引：157

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

页码：65 / 79

页数：15

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