Unveiling the role of immune response and related cytokines in radiation-induced skin injury: orchestrate inflammation to repair or fibrosis

Radiation-induced skin injury (RISI) poses a significant clinical challenge in radiotherapy, characterized by acute inflammatory responses progressing to chronic fibrosis. Central to its pathogenesis is the dynamic interplay between immune cells and cytokine-mediated cascades following DNA double-strand breaks (DSBs) and oxidative stress induced by. This process triggers localized immune activation, radiation-damaged structural cells release DAMPs, triggering resident Langerhans cells and dermal dendritic cells to initiate antigen presentation and cytokine cascades; subsequently, activated macrophages and DCs recruit neutrophils and monocytes, driving acute inflammation that critically determines tissue fate toward regenerative repair or pathological fibrosis. Meanwhile, ultraviolet (UV) radiation primarily drives immunosuppression and photoaging. This review systematically delineates the dual regulatory roles of diverse immune populations—including T lymphocyte subsets, mast cells, and eosinophils—through comprehensive cytokine profiling. We highlight how temporal shifts in immune phenotypes orchestrate inflammation resolution versus fibrotic transformation. By integrating these insights, we provide a mechanistic framework of immune cells and related cytokines for RISI progression.