Contact-dependent regulation of UV-B/C-induced cell fate by neighboring intact cells

High-energy UV light from the UV-B and UV-C ranges induces severe cellular damage that leads to oxidative stress, cellular senescence, and apoptosis. Most studies of such UV-induced phenotypes have been performed in homogeneous cell cultures where all cells were subjected to comparable levels of damage. However, in physiological conditions, UV exposure generates heterogeneous cell populations in which damaged cells coexist with intact neighbors. How such cellular context influences UV-induced outcomes remains insufficiently understood. Here, we examined the effects of intact neighboring cells on mammalian cells exposed to combined UV-B and UV-C radiation. We show that the presence of intact cells enhances the removal and apoptotic progression of cells treated with high doses of UV, while having little effect on the cells exposed to low and moderate doses. Transcriptomic profiling revealed that UV-treated cells grown in co-culture with intact neighbors exhibit a markedly attenuated transcriptional response to UV exposure, including reduced activation of oxidative stress and reparatory pathways, compared to UV-treated cells grown in monoculture. These effects required direct cell-cell contact and were not mediated by diffusible factors, gap junctions, or tunneling nanotubes. Instead, integration of transcriptomic data with ligand-receptor analysis revealed extensive remodeling of intercellular communication profiles under co-culture conditions. Together, these findings reveal a contact-dependent, non-cell-autonomous layer of regulation that shapes cellular responses to severe UV-induced damage and may represent a general principle governing how multicellular environments influence damage resolution.