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