Insights into Effects of Topical Application of Cis-Urocanic Acid on Skin Microbiome and Immune Modulation

Urocanic acid (UCA) is a major chromophore present abundantly in the epidermis. Upon UV exposure trans-UCA is isomerized to cis-UCA, which is known to cause immune suppression via various pathways, such as activation of 5-HT2A receptor and serotonin signaling. However, the effects of cis-UCA on the skin microbiome and innate immune system is not known. We recently showed that skin microbiome modulates the effects of UV on cellular response and immune function. Herein we investigated the effects of cis-UCA on skin microbiome and the innate immune system and its components such as antimicrobial peptides (AMPs) using mouse models. Our results show that UV-A, UV-B and PUVA significantly isomerized UCA compared to control groups. Interestingly, topical application of cis-UCA on shaved dorsal skin significantly modulated the skin microbial communities both at 8h and 24h. The prominent species affected by topical application of cis-UCA were Staphylococcus xylosus (at 8h) and Staphylococcus capitis/caprae and Propionibacterium acnes (at 24h). Additionally, gene expression of various AMPs and cytokines were also affected by cis-UCA. Intriguingly, mice that were disinfected prior to UV exposure showed reduced isomerization of UCA compared to non-disinfected control mice. Finally, using the contact allergy model we confirmed a dose-dependent increase in immune suppression to DNFB when mice were pre-treated with cis-UCA. Taken together, our results show significant effects of cis-UCA on skin microbiome (vice versa) and gene regulation of AMPs, which could play an important role in UV-induced immune suppression.