Cis-urocanic acid, a product formed by ultraviolet B irradiation of the skin, initiates an antigen presentation defect in splenic dendritic cells in vivo.
Urocanic acid (UCA, deaminated histidine) is a major ultraviolet-absorbing component of the stratum corneum. On UV irradiation, the naturally occurring trans form converts to the cis isomer. We have previously postulated that UV-induced systemic suppression is initiated by cis-UCA by way of an antigen-presenting cell defect. To test this hypothesis further, we have investigated the antigen-presenting cell (APC) function of splenic dendritic cells (DC). Splenic DC were prepared from mice 7 days after 1 h UV irradiation (27 kJ/m2) or i.v. administration of 50-200 micrograms/mouse of cis- or trans-UCA. Dendritic cells from UV-irradiated or cis-UCA-treated mice had a significantly impaired (APC) ability, assessed by the proliferative response of purified T cells from mice immune to DNP6 OVA to DC pulsed with this antigen. Dendritic cells from mice given trans-UCA had normal APC ability. The number of FcR+ cells was the same in DCs from all four treatment groups, and the number of IAd+ cells and the intensity of IAd expression were not decreased in DCs from UV-irradiated or cis-UCA-treated mice. Mixture of DCs from UV- or cis-UCA-treated mice with DCs from normal mice did not suppress APC activity. Dendritic cells taken 3 days after UV or cis-UCA treatment, in contrast to DC taken 7 days after treatment, had normal APC ability, indicating a time delay in the generation of the APC defect. In contrast, addition of cis-UCA or trans-UCA (66 micrograms/ml) directly to an in vitro proliferation assay had no effect, suggesting that cis-UCA may be activated in vivo. These results support our original hypothesis that cis-UCA has a natural role as a modulator of immune function.
D000818:Animals; D000941:Antigens / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000528:radiation effects; D000939:Epitopes / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007093:Imidazoles / Q000633:toxicity*; D007108:Immune Tolerance; D051379:Mice; D008807:Mice, Inbred BALB C; D011961:Receptors, Fc / Q000032:analysis; D012867:Skin / Q000276:immunology / Q000528:radiation effects*; D013154:Spleen / Q000276:immunology; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014560:Urocanic Acid / Q000633:toxicity*
D000941:Antigens; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007093:Imidazoles; D011961:Receptors, Fc; D014560:Urocanic Acid