Vitamin A deficiency (VAD) has been linked to compromised resistance to infectious diseases. In countries where early childhood VAD is common, vitamin A supplementation public health programs initiated in the 1980s were shown to reduce the incidence of diarrhea and measles, and all-cause mortality. VAD also increases the risk of immune system over-reaction, leading to chronic inflammation in the intestinal system, stronger allergic reactions and autoimmune diseases.
Lymphocytes and monocytes are types of white blood cells of the immune system. Lymphocytes include natural killer cells, which function in innate immunity, T cells for adaptive cellular immunity and B cells for antibody-driven adaptive humoral immunity. Monocytes differentiate into macrophages and dendritic cells. Some lymphocytes migrate to the thymus where they differentiate into several types of T cells, in some instances referred to as "killer" or "helper" T cells and further differentiate after leaving the thymus. Each subtype has functions driven by the types of cytokines secreted and organs to which the cells preferentially migrate, also described as trafficking or homing.
Reviews based on in vitro and animal research describe the role that retinoic acid (RA) has in the immune system. RA triggers receptors in bone marrow, resulting in generation of new white blood cells. RA regulates proliferation and differentiation of white blood cells, the directed movement of T cells to the intestinal system, and to the up- and down-regulation of lymphocyte function. If RA is adequate, T helper cell subtype Th1 is suppressed and subtypes Th2, Th17 and iTreg (for regulatory) are induced. Dendritic cells located in intestinal tissue have enzymes that convert retinal to all-trans-retinoic acid, to be taken up by retinoic acid receptors on lymphocytes. The process triggers gene expression that leads to T cell types Th2, Th17 and iTreg moving to and taking up residence in mesenteric lymph nodes and Peyer's patches, respectively outside and on the inner wall of the small intestine. The net effect is a down-regulation of immune activity, seen as tolerance of food allergens, and tolerance of resident bacteria and other organisms in the microbiome of the large intestine. In a vitamin A deficient state, innate immunity is compromised and pro-inflammatory Th1 cells predominate.