Modulation of multiple sclerosis by sunlight exposure: role of cis-urocanic acid.

The role of cis-urocanic acid (UCA) as a UV-mediated immunomodulator in MS patients was investigated. Plasma levels of cis-UCA were significantly lower in MS patients compared to controls. Stimulation of MBP- and MOG-specific T cells in the presence of cis-UCA, significantly increased IL-10, and inhibited IFN-γ production. PBMCs cultured in the presence of cis-UCA increased CD4(+)CD25(+)FoxP3(+) regulatory T cell percentages. Dendritic cells cultured in the presence of cis-UCA significantly reduced Ag presentation capacity. Finally, cis-UCA activated the 5-HT2A receptor, inducing the increase in phosphorylated forms of ERK 1/2 and JNK2. Thus, in addition to vitamin D, cis-UCA also appears to be an additional UV-mediated immunomodulator.