Hypoxia-inducible Factor 1 in Dendritic Cells Is Crucial for the Activation of Protective Regulatory T Cells in Murine Colitis

摘要: Dendritic cells (DCs) serve as a bridge between innate and adaptive immunity help to maintain intestinal homeostasis. Inflammatory bowel disease (IBD) is associated with dysregulation of the mucosal immune response. The concomitant hypoxic inflammation in IBD will activate transcription factor hypoxia-inducible factor-1 (HIF-1) also drive gene expression DCs. Recent studies have described protective role for epithelial HIF-1 mouse models IBD. We investigated DC function dextran sodium sulfate (DSS)-induced model murine colitis. Wild-type dendritic cell-specific HIF-1α knockout mice were treated 3% DSS 7 days. Knockout DCs led significantly larger loss body weight DSS-induced colitis than control mice. exhibited more severe increased levels proinflammatory cytokines enhanced production mucin. Induction regulatory T (Tregs) was impaired, number forkhead box P3 (Foxp3) Tregs diminished by knockout. Our findings demonstrate that necessary induction sufficient numbers inflammation.