Vitamin-mediated regulation of intestinal immunity

Abstract

The intestine is exposed continuously to complex environments created by numerous injurious and beneficial non-self antigens. The unique mucosal immune system in the intestine maintains the immunologic homeostasis between the host and the external environment. Crosstalk between immunocompetent cells and endogenous (e.g., cytokines and chemokines) as well as exogenous factors (e.g., commensal bacteria and dietary materials) achieves the vast diversity of intestinal immune functions. In addition to their vital roles as nutrients, vitamins now also are known to have immunologically crucial functions, specifically in regulating host immune responses. In this review, we focus on the immunologic functions of vitamins in regulating intestinal immune responses and their roles in moderating the fine balance between physiologic and pathologic conditions of the intestine.

Keywords: IgA; allergy; inflammation; intestinal immunity; regulatory T cells; vitamin.

Figure 1

Regulation of cell trafficking, differentiation, and function by the vitamin A metabolite retinoic acid. CD103⁺ dendritic cells (DCs) express retinaldehyde dehydrogenases (RALDH) by GM-CSF, IL-4, TLR ligand, and retinoic acid (RA), which enable them to convert vitamin A into RA. RA then induces CCR9 and α4β7 integrin in T and B cells, causing them to migrate into the intestine. In addition, retinoic acid affects cell differentiation, such as the preferential differentiation of T cells into regulatory T (T_reg) cells and B cells into IgA-producing plasma cells (PCs). RA also enhances IL-22 production from γδT cells and innate lymphoid cells.

Figure 2

Vitamin B9 is required for the survival of regulatory T cells and subsequent maintenance of immunologic homeostasis in the intestine. Once naïve T cells differentiate into regulatory T (T_reg) cells, they express folate receptor 4 (FR4), and require vitamin B9 for their survival. The absence of sufficient amounts of vitamin B9 induces the apoptosis of T_reg cells, with decreased expression of Bcl-2 and subsequent increased intestinal inflammation.

Figure 3

Vitamin D mediates innate and acquired immunity. The active form of vitamin D, it metabolite 1,25-dihydroxyvitamin D, inhibits the maturation of dendritic cells (DCs) and their production of IL-12 but simultaneously promotes their production of IL-10. In addition, T cells respond directly to 1,25-dihydroxyvitamin D for their preferential differentiation into T_reg cells. As a component of innate immunity, 1,25-dihydroxyvitamin D promotes the production of anti-microbial peptides (AMP) by macrophages and Paneth cells.