Trans-urocanic acid, a natural epidermal constituent, inhibits human natural killer cell activity in vitro.

UV irradiation has been reported to influence NK cell function both in vitro and in vivo. Since urocanic acid may mediate UV-induced immune modulation we tested the effect of trans- and cis-urocanic acid (UCA) on the cytotoxic activity of human peripheral blood lymphocytes against the erythroleukemic target cell line K562 in vitro. Trans-UCA was found to be a strong inhibitor of NK cell activity whereas cis-UCA had no effect. Trans-UCA also partially inhibited cytotoxic function of IL-2-activated NK cells and reduced IL-2-induced activation of NK cells. This is the first report describing trans-UCA to be active, and cis-UCA inactive, in regulating an immune function. In the skin, a decrease in epidermal trans-urocanic acid concentration by UV radiation could produce a favorable milieu for NK cell activity, and thus counteract the impairment of antigen-specific immune surveillance, induced by increased cis-urocanic acid concentrations.