Vitamin A and retinoic acid in T cell-related immunity

Interest in vitamin A as a regulator of immune function goes back to the early 1900s. Recently, several lines of evidence have converged to show that retinoic acid (RA), a major oxidative metabolite of vitamin A, plays a key role in the differentiation of T cell subsets, the migration of T cells into tissues, and the proper development of T cell-dependent antibody responses. This review discusses evidence from experimental studies that RA promotes the differentiation of regulatory T cells, which help to suppress inflammatory reactions, and plays a significant role in normal mucosal immunity by modulating T cell activation and regulating cell trafficking. RA also promotes antibody responses to T cell-dependent antigens. Conversely, in a state of vitamin A deficiency, inflammatory T cell reactions may be inadequately opposed and therefore become dominant. Although data from human studies are still needed, the framework now developed from studies in mice and rat models suggests that adequate vitamin A status, whether derived from ingestion of preformed retinol or β-carotene, is important for maintaining a proper balance of well-regulated T cell functions and for preventing excessive or prolonged inflammatory reactions.