Chronic Inflammation in Irradiated Mouse Mammary Glands: A Transcriptome Sequencing Analysis.

Abstract

Normal tissues exposed to radiation during radiotherapy or radiation accidents are susceptible to chronic inflammation, which poses a significant health concern. Here, we used the mouse mammary gland as a model to investigate radiation-induced damage to normal tissue. Five-week-old mice were chosen to capture the radiation-sensitive pubertal developmental window, and transcriptomic sequencing was used to profile gene expression changes at 1-5 months postirradiation. Single-cell RNA sequencing was performed to identify immune cell populations and characterize their transcriptional features at the subpopulation level. By combining transcriptomic data with morphological analysis of the irradiated mammary gland, we identified gene expression signatures of specific macrophage and T cell subtypes within the postirradiation microenvironment and highlighted their roles in modulating inflammation and maintaining cell junction homeostasis. Notably, dysregulation of adipocyte differentiation and lipid metabolism pathways was observed as early as 1 month postirradiation, and this metabolic disturbance was associated with persistently elevated oxidative stress in the tissue. Single-cell analysis showed that CD163+ macrophages were functionally enriched in lipid metabolism pathways, and immunofluorescence staining confirmed their significant accumulation in the irradiated mammary gland. Overall, these findings suggest that CD163+macrophages are key mediators of chronic tissue inflammation after irradiation. This study offers a comprehensive characterization of microenvironmental changes in the irradiated mammary gland and identifies potential targets for radioprotection strategies to modulate tissue microenvironment factors.