A novel role for the regulatory NRP1 in immune and inflammatory reactions during radiation-induced lung injury.

Neuropilin-1 (NRP1) is a transmembrane protein with diverse functions in tumor biology and immune system regulation. Despite extensive research, its specific function in radiation-induced lung injury (RILI) remains unclear. In this study, we aimed to explore the influence of NRP1 on immune and inflammatory responses mediated by regulatory T cells (Tregs) in RILI. Initial findings revealed that radiation increases the number of NRP1-expressing Tregs, which correlated with RILI severity. Inhibiting Tregs in mice effectively suppressed radiation-induced Treg differentiation and promoted helper T cell 1 (Th1) and Th2 cytokine expression, thereby shifting T cell polarization toward a Th1 phenotype and slowing RILI progression. However, Treg inhibition alone did not entirely prevent RILI, as skin damage and inflammatory factor expression persisted. Subsequent specific NRP1 knockdown in alveolar epithelial cell-II altered the inflammatory gene network, suppressed TGF-β signaling, reduced Treg levels, decreased IL-17 A and INF-γ expression, and shifted Th cell polarization toward Th2, alleviating RILI. In conclusion, this study reveals a novel mechanism by which NRP1 regulates immune and inflammatory responses in RILI, offering a promising avenue for developing innovative therapeutic strategies.