Vitamin effects on the immune system: vitamins A and D take centre stage
J. Rodrigo Mora, Nature Reviews Immunology volume 8, pages685–698(2008)
Key Points
The metabolites of vitamins A and D, retinoic acid and 1,25(OH)2VD3, respectively, bind to nuclear receptors and exert potent and specific immunomodulatory effects.
The vitamin D metabolite 1,25(OH)2VD3 inhibits T-helper 1 (TH1)- and enhances TH2-cell responses. It also decreases TH17-cell differentiation, with reciprocal upregulation of forkhead box protein 3 (FOXP3)+ regulatory T (TReg) cells and T regulatory type 1 (TR1) cells.
1,25(OH)2VD3 also inhibits the proliferation of B cells and their differentiation into antibody-secreting cells. Part of this effect might be indirect by decreasing T-cell help.
1,25(OH)2VD3 modulates dendritic cell (DC) function by impairing their maturation and enhancing their capacity to generate TR1 cells. By contrast, 1,25(OH)2VD3 enhances the bactericidal capacity of macrophages.
The vitamin A metabolite retinoic acid induces TH2-cell responses. It also inhibits TH17-cell differentiation and, reciprocally, potentiates TReg-cell development.
Retinoic acid is synthesized by gut-associated DCs and induces the expression of gut-homing receptors α4β7-integrin and CC-chemokine receptor 9 (CCR9) by lymphocytes following activation. Conversely, retinoic acid blocks the upregulation of skin-homing receptors. Retinoic acid is also involved in the differentiation of IgA-secreting B cells in the gut.
Given its potent immunomodulatory properties, 1,25(OH)2VD3 analogues are currently being tested in autoimmune diseases and as adjuvants for immunosuppressive therapy in transplantation.
Abstract
Vitamins are essential constituents of our diet that have long been known to influence the immune system. Vitamins A and D have received particular attention in recent years as these vitamins have been shown to have an unexpected and crucial effect on the immune response. We present and discuss our current understanding of the essential roles of vitamins in modulating a broad range of immune processes, such as lymphocyte activation and proliferation, T-helper-cell differentiation, tissue-specific lymphocyte homing, the production of specific antibody isotypes and regulation of the immune response. Finally, we discuss the clinical potential of vitamin A and D metabolites for modulating tissue-specific immune responses and for preventing and/or treating inflammation and autoimmunity.