| First Author | Kashiwagi I | Year | 2015 |
| Journal | Immunity | Volume | 43 |
| Issue | 1 | Pages | 65-79 |
| PubMed ID | 26141582 | Mgi Jnum | J:259037 |
| Mgi Id | MGI:6142002 | Doi | 10.1016/j.immuni.2015.06.010 |
| Citation | Kashiwagi I, et al. (2015) Smad2 and Smad3 Inversely Regulate TGF-beta Autoinduction in Clostridium butyricum-Activated Dendritic Cells. Immunity 43(1):65-79 |
| abstractText | 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-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-beta1 from lamina propria dendritic cells (LPDCs). C. butyricum-mediated TGF-beta1 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 colitis models. 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. |
