Characterization of Human Fetal Intestinal Dendritic Cells

The gastro-intestinal tract harbors 10¹⁴ commensal bacteria, but also an active immune system to challenge harmful pathogens. Disturbance of this fine balance contributes to the development of inflammatory bowel disease (IBD) via the induction of commensal-specific T cell-mediated immune responses. T cell responses are initiated by antigen-presenting dendritic cells (DCs) that sense and take-up microbes in the tissues that line epithelia. In adults, 3 different intestinal DC subsets have been defined, CD103+CD141+SIRPα- cross-presenting DCs, CD103+ SIRPα+ tolerogenic DCs and CD103-SIRPα+ DCs of which the function is less clear. However, the development of human intestinal lamina propria DCs remain poorly understood. Here, we analyzed the phenotype and function of the human fetal gut DCs. Our preliminary results show that  CD103+CD141+SIRPα- subset is absent in human fetal intestinal lamina propria, while this subset is an important cross-presenting cells in the adult human gut. CD103- SIRP α- dendritic cells are abundantly present in fetal gut, which is absent in adult human gut, which may be precursors of various mucosal DC subsets. Meanwhile, fetal intestinal DCs only produce cytokines in response to PGN, but not to LPS and poly(I:C). CD103-SIRP α+ subset is able to produce more cytokines and more capable to induce proliferation in  naïve CD4+ T cells than the other two subsets. The understanding of the role of these subsets and the development of human intestinal DCs will help to define strategies for the treatment of intestinal pathologies and contribute to improved design of mucosal vaccines.