Comparative Multi-Omics Highlights Inflammatory Monocyte-Derived Dendritic Cells as Key Mediators of UVB-Induced Photosensitivity

This study investigates the mechanisms behind the differing responses to UV radiation in skin conditions, using a multi-omics approach to compare photosensitive disorders (CLE and DM) with photoresponsive conditions (psoriasis and vitiligo). The research identifies monocyte-derived dendritic cells (moDCs) as key mediators of photosensitivity, particularly in CLE and DM, where they are found in lesional skin alongside cytotoxic CD4+ T cells. These moDCs express high levels of MMP9, which degrades collagen IV, facilitating immune cell infiltration and enhancing dermatitis. The study also shows that keratinocytes preconditioned with IFN-β are more susceptible to UVB-induced cell death, releasing factors that activate moDCs and create a feedback loop of immune activation and tissue damage. Targeting MMP9 or moDC recruitment pathways could be a potential therapeutic strategy to reduce UV-induced inflammation in photosensitive skin disorders.