Role of mucosal dendritic cells in inflammatory bowel disease

Abstract

The gastrointestinal innate and adaptive immune system continuously faces the challenge of potent stimuli from the commensal microflora and food constituents. These local immune responses require a tight control, the outcome of which is in most cases the induction of tolerance. Local T cell immunity is an important compartment of the specific intestinal immune system. T cell reactivity is programmed during the initial stage of its activation by professional presenting cells. Mucosal dendritic cells (DCs) are assumed to play key roles in regulating immune responses in the antigen-rich gastrointestinal environment. Mucosal DCs are a heterogeneous population that can either initiate (innate and adaptive) immune responses, or control intestinal inflammation and maintain tolerance. Defects in this regulation are supposed to lead to the two major forms of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC). This review will discuss the emerging role of mucosal DCs in regulating intestinal inflammation and immune responses.

Figure 1

Bacterial and food antigens are continuously surveyed by the mucosal immune system, processed and transported via the lymph to mesenteric lymph nodes or via the portal vein to the liver. DCs present processed luminal antigens to naïve T cells to achieve tolerance or to initiate host defence to pathogens.

Figure 2

DCs continuously survey the intestinal lumen, phagocytose and process luminal antigens and present them to T cells, which will differentiate in presence of IL-6 and TGF-β to IL-17A and IL-17F producing TH17 cells, in presence of IL-12 and IFN-γ into TH1 cells or in presence of IL-4 into TH2 cells. nTreg, natural occurring regulatory T cell; iTreg, inducible regulatory T cells; Tr1, regulating T cell.