Fig. 1

Overview of the intestinal immune system. Innate immunity: Intestinal epithelial cells provide a physical barrier between the luminal microbes and the underlying intestinal tissues to control defense and tolerance. Specialized epithelial cells produce a mucus layer (goblet cells) and secrete antimicrobial proteins (Paneth cells) that limit bacterial exposure to the epithelial cells. Production of large amounts of immunoglobulin (Ig) A provides additional protection from luminal microbiota. Innate microbial sensing by epithelial cells, dendritic cells, and macrophages is mediated through pattern recognition receptors and induces various pathways that mediate microbial killing and activate adaptive immune cells. Adaptive immunity: Dendritic cells present antigens to naïve CD4 positive (+) T cells in secondary lymphoid organs (mesenteric lymph nodes), where factors such as the phenotype of the antigen-presenting cells and cytokine milieu modulate differentiation of proinflammatory T helper (Th) cell subsets (Th1, Th17) with characteristic intestinal homing profiles and cytokines such as interleukin (IL)-17, IL-22, tumor necrosis factor alpha (TNFα), and interferon gamma (IFNγ). Defense mechanisms that limit microbial entry into intestinal tissues also serve as a mechanism of tolerance. Activation of unique populations of dendritic cells in the intestinal lamina propria does not result in secretion of proinflammatory cytokines. Those dendritic cells present antigen to T cells in mesenteric lymph nodes, which leads to differentiation of regulatory (Treg) and anti-inflammatory (Th2) T cell populations, mediated by transforming growth factor beta (TGFß), IL-4, IL-10, and IL-13