400 Isomerization of urocanic acid by ultraviolet radiation and its role in modulation of skin microbiome, antimicrobial peptides, and immune function

Trans-urocanic acid (UCA) is a natural photoreceptor present in the stratum corneum of the skin. Upon exposure to ultraviolet-radiation (UV-R), trans-UCA is isomerized to cis-UCA. Several studies indicate that cis-UCA induces local and systemic immune suppression via various underlying mechanisms. However, microbes are established all over the surface of the skin and the interplay between cis-UCA and the skin microbiome is not completely understood. In this study, we investigated the effects of cis-UCA on the skin microbiome and antimicrobial peptides (AMPs) expression using mouse models. We employed HPLC to determine quantitative isomerization of trans-UCA to cis-UCA by UV-R. We further made use of the model of contact allergy to assess the percentage of immune suppression by UV-A, UV-B, PUVA and cis-UCA to the contact allergen DNFB. Next, we treated mice with UV-A, UV-B, PUVA and cis-UCA and performed 16S rRNA gene sequencing for microbiome analysis and qPCR for AMPs gene expression. We noted that UV-B (p=0.002) and PUVA (p=0.023) significantly increased the formation of cis-UCA, whereas UV-A exposure alone showed no significant formation of cis-UCA in the skin. Utilizing the contact allergy model, we observed a dose-dependent increase in immune suppression (by up to 100%) against the contact allergen DNFB, when mice were pretreated with cis-UCA. Furthermore, application of cis-UCA on the skin altered the microbial landscape of the skin both at 8h and 24h, correlating with a change in expression of various AMPs. Collectively our results suggest that cis-UCA alters the skin microbial landscape and AMP expression. This imbalance in the skin microbial landscape and altered AMP expression may be crucial in immune suppression upon UV-R exposure mediated through cis-UCA.