Ayaka Okazaki, Hisayoshi Imanishi, Hiroyuki Kunimoto, Daisuke Tsuruta
Targeted phototherapy using 308-nm excimer light (EL-308) is widely employed to treat localized skin diseases, such as psoriasis and vitiligo. Although its immunomodulatory effects are well established, tissue-level epidermal responses to EL-308 in human skin explants have not been fully characterized in a controlled ex vivo setting. Therefore, the present study examined dose- and time-dependent changes in keratinocyte proliferation, apoptosis, and differentiation markers in a human organ-cultured skin model without systemic immune inputs (i.e., without circulation-dependent immune-cell recruitment). Human organ-cultured skin samples were irradiated with EL-308 at 300, 400, or 600 mJ/cm2 and analyzed on days 2, 5, and 7 using immunohistochemical markers, including Ki-67, TUNEL, CK10, CK16, involucrin, and integrin β1. RNA sequencing was performed 24 h after irradiation with 600 mJ/cm2, followed by KEGG and GO enrichment analyses. EL-308 exposure was associated with dose- and time-dependent changes in Ki-67 and TUNEL labeling and with altered expression of differentiation-related markers (integrin β1, CK16, CK10, and involucrin). Transcriptomic analyses revealed enrichment of metabolic and epidermis-related gene sets, including keratinization and epidermal development terms, consistent with a tissue-level response to UVB exposure. These findings provide descriptive data on epidermal marker dynamics and associated transcriptional programs after EL-308 irradiation in human organ-cultured skin and may inform future studies designed to evaluate early damage markers and functional outcomes.