International Session (Symposium)2(JSGE・JSH)
November 4 (Fri.), 9:00–12:00, Room 8 (Portopia Hotel Main Building Kairaku 2)
Role of E-Cadherin of Dendritic Cells in Colonic Homeostasis
- Department of Gastroenterology, The University of Tokyo
BACKGROUND: TGF-β has been reported to limit E-cadherin expression of dendritic cells (DCs). Here we investigated the role of DC's E-cadherin in colonic homeostasis associated with TGF-β signaling and microbial communities.METHODS: We used mice with DC-specific deletion of TGF-β signaling (CD11c-Cre Tgfbr2fl/fl) and E-cadherin (CD11c-Cre Cdh1fl/fl). Fecal DNA from CD11c-Cre Tgfbr2fl/fl and Cre-negative control mice was used for 16S rRNA next-generation pyrosequencing analysis. E-cadherin expression was analyzed by flow cytometry, qPCR, and immunoblotting. To analyze the effect of TGF-β signaling on E-cadherin expression, we examined E-cadherin expression of BMDCs with in vivo deletion of TGF-β signaling using Cre-expressing-adenoviral and Tgfbr2-shRNA-lentiviral approaches. CD11c-Cre Cdh1fl/fl and control mice were treated with dextran-sulfate-sodium (DSS).RESULTS: CD11c-Cre Tgfbr2fl/fl mice showed spontaneous colitis with enhanced E-cadherin expression in intestinal DCs. In vitro, E-cadherin expression of BMDCs was also upregulated by inhibiting TGF-β signaling. Principal-component analysis of 16S rRNA transcripts showed that marked separation of microbial composition between CD11c-Cre Tgfbr2fl/fl and control mice. In family-level analysis of 16S rRNA pyrosequencing, the expansion of Enterobacteriaceae was the most significant change in CD11c-Cre Tgfbr2fl/fl microbial communities. CD11c-Cre Cdh1fl/fl mice treated with DSS exhibited significantly attenuated the sign of colitis compare with controls, suggesting E-cadherin+ DCs are proinflammatory.CONCLUSIONS: E-cadherin expression and TGF-β signal loss of DCs are associated with the development of dysbiosis and colitis. Blocking of DC's E-cadherin may have therapeutic potential for IBD.
- Index Term 1: E-cadherin
- Index Term 2: Dendritic cell