Vitamin A
The role of vitamin A and its metabolites in the immune system and host susceptibility is discussed in a series of reviews [77, 78]. This nutrient is involved in normal differentiation of epithelial tissue, furthermore retinoic acid is essential for imprinting T and B cells with gut-homing specificity and T array cells and IgA cells in intestinal tissues [79], thus enhancing the intestinal immune response and supporting the intestinal barrier [80]. Carotenoids (both provitamin A and non-provitamin A carotenoids) have immunoregulatory actions including the reduction of the toxic effects of ROS and the regulation of membrane fluidity and gap-junctional communication [81].
Vitamin A deficiency impairs barrier function, impairs immune responses and increases susceptibility to a variety of infections. Furthermore, many aspects of innate immunity, in addition to barrier function, are affected by vitamin A. For example, vitamin A regulates the number and function of NK cells [82], contributes to the phagocytic and oxidative activity of the macrophage burst [79] and controls the maturation of neutrophils and its deficiency [83]. The activity of natural killer cells is therefore reduced by vitamin A deficiency. The impact of vitamin A on acquired immunity is however clear since it is involved in the development and differentiation of Th1 and Th2 cells [62, 79]. Moreover there is evidence that vitamin A deficiency alters the balance of Th1 and Th2 cells, decreasing the Th2 response, without affecting or, in some cases, enhancing the Th1 response. This suggests that vitamin A increases the Th1 cell average in immunity [84]. However, studies in several experimental models have shown how the retinoic acid metabolite of vitamin A reduces the responses of Th1-type cells (cytokines, cytokine receptors and the transcription factor T-bet, which promotes Th1), improving responses to Th2-type cells (cytokines and Th2-favoring transcription factor GATA-3) [62]. Indeed, it maintains the normal Th2 response mediated by antibodies by suppressing the production of IL-12, TNF-α and IFN-γ by Th1 cells [85]. Vitamin A appears to be important in the differentiation of regulatory T lymphocytes by suppressing Th17 differentiation, which have implications for the control of adverse immune reactions [86]. It helps regulate the production of IL-2 and the pro-inflammatory TNF-γ, which activates the phagocytic and oxidative action of the macrophages activated during inflammation [79]. It ensures the normal functioning of B lymphocytes, necessary for the generation of antibody responses to the antigen [85].
Retinoic acid appears to promote the movement of T cells to gut-associated lymphoid tissue and, interestingly, some gut-associated immune cells are able to synthesize retinoic acid [87]. Vitamin A deficiency is associated with increased morbidity and mortality in children and appears to predispose to respiratory infections, diarrhea and severe measles [88, 89]. Moreover, supplementing vitamin A in deficient children improves recovery from infectious diseases and reduces mortality [78, 90]. The Recommended Dietary Allowance (RDA) for vitamin A reports a range of 900–700 µg/day [91].