The yin and yang of intestinal epithelial cells in controlling dendritic cell function

Abstract

Recent work suggests that dendritic cells (DCs) in mucosal tissues are "educated" by intestinal epithelial cells (IECs) to suppress inflammation and promote immunological tolerance. After attack by pathogenic microorganisms, however, "non-educated" DCs are recruited from nearby areas, such as the dome of Peyer's patches (PPs) and the blood, to initiate inflammation and the ensuing immune response to the invader. Differential epithelial cell (EC) responses to commensals and pathogens may control these two tolorogenic and immunogenic functions of DCs.

Figure 1.

Gut mucosal immune cells involved in the “steady-state” and during infection. (Left) Steady-state. TSLP and possibly TGF-β released by ECs “condition” noninflammatory resident DCs (including the CX3CR1⁺ subtype), which extend processes into the intestinal lumen. These cells allow sampling and presentation of harmless commensal bacteria and may be involved in tolerance induction under homeostatic conditions or in innate defense in response to mucosal pathogens. These cells are generally noninflammatory and drive the development of Th2 or T reg cells and B cell class switch recombination (CSR). (Right) Pathogen infection. During infection, invasive pathogens can induce the release of inflammatory mediators, including IL-8 and CCL20. To initiate protective immunity, a pool of fully competent DCs able to respond quickly to bacteria is required. CCR6⁺ DCs in the PPs are a reservoir of non-educated DCs that can be rapidly recruited during infection.