Role of different dendritic cell subsets in vivo

To understand the roles of various gut dendritic cell (DCs) subsets in controlling intestinal inflammation, two DTR mice strains: Clec9A DTR and Clec4a4 DTR, capable of conditional in vivo ablation of respective colonic CD103+ CD11b- and CD103+ CD11b+ DCs have been generated. In a dextran sodium sulphate (DSS) model of colonic inflammation, ablation of CD103+ CD11b- colonic DCs resulted in exacerbated colitis, while ablation of colonic CD103+ CD11b+ DCs resulted in resistance to colitis when subjected to the same DSS regiment. Hence our results highlight the opposing roles of these two distinct colonic DC subsets in controlling DSS-induced colonic inflammation. A cross-talk between DCs, other gut immune cells and the colonic epithelia, involved in maintenance of a functional mucosal epithelial barrier, has been proposed to directly impact outcome of colonic inflammation. The mechanistic details of how these distinct DC subsets contribute to regulate colonic inflammation will be discussed.DOCTOR OF PHILOSOPHY (SBS