Regulation of intestinal dendritic cell function by SIRP?. (360G-Wellcome-096988_Z_11_Z)

This project will explore how signal regulatory protein ? (SIRP?) regulates dendritic cell function in the intestine. Previous work has identified SIRP?+and SIRP?- subsets of dendritic cells (DC) in mouse and human intestine, and has suggested that these DC may play distinct roles in driving effector immuneresponses or tolerance. Mice with a non-signalling mutant form of SIRP have reduced numbers of CD103+CD11b+ DC in the intestine, as well as fewer IL-17 producing CD4+ T-cells, a population which plays important roles in controlling the intestinal microbiota and in inflammatory bowel diseases. Here we will characterise fully the functions and localisation of SIRP + and SIRP - subsets of intestinal DC, will identify the cells expressing CD47, the ligand for SIRP + and will determine how SIRP might influence other myeloid cells in different parts of the intestine. Using SIRP mutant DC and by ligating SIRP in vitro, we will examine directly how SIRP? modifies DC activation and will explore the signalling pathways involved. By comparing these parameters in steady state and after administration of adjuvants with