Urocanic acid (UCA) is one of the key mediators of ultraviolet radiation (UVR)- induced immune suppression in the skin. Skin resident microbes are known to metabolize trans- and cis-UCA, and potentially modulate the subsequent immune response. In the present study we investigated whether skin microbiome can regulate cis-UCA mediated immune suppression. Using 16s rRNA sequencing, we show that cis-UCA application results in significant changes in microbial population, where certain microbes could thrive by utilizing UCA (UCA+). To confirm utilization of UCA by skin microbiome, we applied cis-UCA to wild-type and disinfected mice and, and quantified cis-UCA at various timepoints by mass spectrometry . Our results show increased utilization of cis-UCA in presence of microbiome. Furthermore, using skin inflammation murine models and immune assays, we show that presence of skin microbiome limits immunosuppressive capacity of cis-UCA. To understand the underlying mechanisms of skin microbiome regulation of cis-UCA mediated immune response, we performed transcriptomic analysis of cis-UCA treated skin, which shows acute gene regulation and activation of multiple immune response pathways. Our current hypothesis and ongoing work are that UCA+ microbial species interfere with cis-UCA mediated gene regulation in the skin, thus affecting its immunosuppressive capacity. Taken together, our results demonstrate that skin microbiome regulates cis-UCA mediated immune suppression.

ESDR231 - cis-urocanic acid mediated cutaneous immune suppression is controlled by microbiome.

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING