Vitamin A-treated natural killer cells reduce interferon-gamma production and support regulatory T cell differentiation

Abstract

NK cells are innate cytotoxic lymphocytes that contribute to immune responses against stressed, transformed or infected cells. The effector functions of NK cells are regulated by microenvironmental factors, including cytokines, metabolites and nutrients. Vitamin A is an essential micronutrient that plays an indispensable role in embryogenesis and development, but was also reported to regulate immune responses. However, the role of vitamin A in regulating NK cell functions remains poorly understood. Here, we show that the most prevalent vitamin A metabolite, all-trans retinoic acid (atRA), induces transcriptional and functional changes in NK cells leading to altered metabolism and reduced IFN-γ production in response to a wide range of stimuli. atRA-exposed NK cells displayed a reduced ability to support dendritic cell (DC) maturation and were inefficient in eliminating immature DCs. Moreover, they supported the polarization and proliferation of regulatory T cells. These results imply that in vitamin A-enriched environments, NK cells can acquire regulatory-like functions and might support tolerogenic immunity and/or immunosuppression.