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 (p¼0.002) and PUVA (p¼0.023) 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.

In order to suppress self-reactive T cells that escape from central tolerance, additional mechanism in peripheries, so-called peripheral tolerance, is essential; however this mechanism is not fully elucidated. To investigate this issue, here we generated a novel murine transgenic line that expressed membrane-bound ovalbumin (mOVA) under the control of human involucrin (Ivl) promoter; Ivl-mOVA mice. Within one week after the transfer of CD8 + T cells from OT-I mice (OT-I T cells), GVHD-like cutaneous and mucosal eruptions developed. Histological analysis revealed massive infiltration of OT-I T cells to the epidermis. Intriguingly, most (>95%) of the transferred OT-I T cells were deleted in lymph nodes within 24 h, and subsequent extensive expansion of OT-I T cells was observed 48 h post transfer. This expansion was observed not only in skin-draining lymph nodes but also in mesenteric lymph nodes, spleen, and bone marrow. We used bone-marrow chimeric mice reconstituted with b2-microglobulin-deficient mice, which lack functional MHC class I, to identify the responsible cell subset for initial deletion of OT-I T cells. OT-I T cell deletion was observed even in these chimeric mice. This result indicates the essential role of radio-resistant cells, suggestive of stromal cells, in secondary lymphoid organs. Taken together, these results suggest that tissue-specific self-antigens presented by radio-resistant lymph node stromal cells control peripheral tolerance and development of GVHD-like skin lesion.

We present a case of Panton‐Valentine leucocidin‐positive methicillin‐susceptible Staphylococcus aureus infection in a couple. The isolated bacterium was not methicillin‐resistant but was very closely related to the USA300 clone.