Immunity and Tolerance Induced by Intestinal Mucosal Dendritic Cells

Abstract

Dendritic cells present in the digestive tract are constantly exposed to environmental antigens, commensal flora, and invading pathogens. Under steady-state conditions, these cells have high tolerogenic potential, triggering differentiation of regulatory T cells to protect the host from unwanted proinflammatory immune responses to innocuous antigens or commensals. On the other hand, these cells must discriminate between commensal flora and invading pathogens and mount powerful immune response against pathogens. A potential result of unbalanced tolerogenic versus proinflammatory responses mediated by dendritic cells is associated with chronic inflammatory conditions, such as Crohn's disease, ulcerative colitis, food allergies, and celiac disease. Herein, we review the dendritic cell population involved in mediating tolerance and immunity in mucosal surfaces, the progress in unveiling their development in vivo, and factors that can influence their functions.

Figure 1

Intestinal mucosal dendritic cell and macrophage development and function. Bone marrow resident Granulocyte Macrophage Progenitors (GMP) give rise to Macrophage DC Precursors (MDP). In turn, CDP give rise to peripheral blood monocytes (Mono) and Common DC Progenitors (CDP). Monocytes will migrate to the lamina propria differentiating into CD11b+CX3CR1+ macrophages that directly sample antigens from the intestinal lumen. On the other hand, CDP will give rise to three subpopulations of intestinal lamina propria DCs: CD11b+CD103+, CD11b−CD103+, and CD11b−CD103−. The former two subsets are responsible for sampling antigen and priming naïve T cells into regulatory T cells (Treg) or IL17-producing T cells (Th17).