538 Acute UVR exposure has prolonged impact on eicosanoid and immune profile of healthy human skin in vivo: Implications for resolution biology

UVR-induced inflammation is characterised by erythema, pain and oedema followed by immunosuppression. While the mechanisms responsible for the peak of UVR-inflammation have been extensively investigated, the long term cellular infiltrate and immune mediators that contribute to resolution or post-resolution phases are unknown in humans. To investigate this in vivo, photoprotected human skin was exposed to 3xMED broadband UVR (N=13;20-58y,phototype I-III) with biopsies and suction blister fluid collected for up to 14-days post-UVR. Quantitative histology was used to determine immune infiltrate levels and phenotype, with LC-MS/MS to profile eicosanoids. This identified at day-1 post-UVR that pro-inflammatory cells (neutrophils, M1 macrophages) and eicosanoids (e.g. PGE2 and 12-HETE) were elevated. By day 4, we detected clearance of neutrophils, accumulation of anti-inflammatory M2-macrophages and normalised prostanoid levels, consistent with cellular resolution. Next we examined the adaptive immune response and detected a significant increase in CD4+ cells up to day-10 post-UVR (P<0.01). This infiltrate comprised of CD4+FOXP3+ Treg-cells and CD4+GATA3+ Th2-cells, with Th2-cells being the dominant phenotype at day-7 post-UVR (70%,P<0.001). In addition, CD8+ T-cells remained significantly elevated throughout the time-course (P<0.05) and almost exclusively consisted of the CD8+ dysfunctional phenotype (CD8+GATA3+) at day-14 post-UVR (80%,P<0.01). Notably, following the initial resolution of UVR-inflammation, prostanoids (e.g. PGF class) showed a gradual increase in expression between days 7 and 14 post-UVR, which may indicate an active role in post-resolution processes. This collectively demonstrates that a single exposure of UVR has long-lasting effects on both immune phenotype and tissue microenvironment, which could contribute to immunosuppression. Targeting these changes provides a novel strategy to enhance resolution and abrogate skin hazards associated with UVR exposure.