Regulation of intestinal immune system by dendritic cells

Abstract

Innate immune cells survey antigenic materials beneath our body surfaces and provide a front-line response to internal and external danger signals. Dendritic cells (DCs), a subset of innate immune cells, are critical sentinels that perform multiple roles in immune responses, from acting as principal modulators to priming an adaptive immune response through antigen-specific signaling. In the gut, DCs meet exogenous, non-harmful food antigens as well as vast commensal microbes under steady-state conditions. In other instances, they must combat pathogenic microbes to prevent infections. In this review, we focus on the function of intestinal DCs in maintaining intestinal immune homeostasis. Specifically, we describe how intestinal DCs affect IgA production from B cells and influence the generation of unique subsets of T cell.

Keywords: Dendritic cells; Gut; Regulatory T cells; Secretory IgA; Th17.

Figure 1

Regulatory T cells induced by intestinal DCs. Intestinal DCs can take up antigen indirectly through M cell-dependent (1), Goblet cell-dependent (2), and neonatal Fc receptor (FcRn)-dependent (3), and apoptosis-dependent manner (4). Alternatively, intestinal DCs can sample luminal antigen using intraepithelial dendrites (5). CX3CR1⁺ phagocytes facilitate the surveillance of circulatory antigens (6). Under steady-state conditions, CD103⁺ DCs induce Foxp3⁺CD4⁺ Tregs using retinoic acid by delivering luminal innocuous antigen. CX3CR1⁺ phagocytes can induce CD8⁺ Tregs to both luminal and circulatory antigens. These cells can expand the Foxp3⁺CD4⁺ Treg populations by IL-10 secretion in the intestinal lamina propria. Plasmacytoid DCs can produce IL-10 in response to TLR2.

Figure 2

Helper T cell induced by intestinal DCs. CD103⁺CD11b⁺ DCs and TLR5⁺ DCs induce T_H17 cells. TLR5⁺ DCs and CD103⁺CD8α⁺ DCs can induce T_H1 cells by means of TLR signaling. CD103⁺CD8α⁺ DCs can also induce CTL. Induced helper T cell and CD8⁺ T cells confer host defense and further inflammation. Intraepithelial CD103⁺ DCs and CX3CR1⁺ phagocytes can sample pathogenic bacteria by extending long dendrites across the epithelium to directly defend against bacterial infection. CD103⁺CD11b⁺ DCs produce IL-23 and IL-22 to promote anti-microbial peptide production from Paneth cells.

Figure 3

Intestinal DCs support secretory IgA generation. Gut CD103⁺CD11b⁺ DCs, Tip DCs, and TLR5⁺ DCs express RALDH2 that is converted into retinoic acid from dietary vitamin A and can be used for IgA production. Gut pDCs and Tip DCs induce IgA generation from B cells by expressing BAFF and APRIL. Eosinophils promote IgA production by expressing BAFF and APRIL or support the function of CD103⁺ DCs.