Recently, a team led by Professor Yiming Zhang of Army Medical University Xinqiao Hospital, Fazhi Qi of Fudan University Zhongshan Hospital, and Professor Junli Zhou of Southern Medical University 10th Affiliated Hospital (Dongguan People’s Hospital) focused on the regulatory mechanism of macrophage function in radiation-induced skin damage and systematically elucidated the important role of TREM2 in maintaining macrophage survival and promoting skin repair under radiation stress. This study demonstrated that irradiation activates the ROS-NRF2-ADAM17 axis that mediates TREM2 shedding, leading to increased macrophage apoptosis and impaired repair function. In contrast, supplementation with TREM2+ macrophages significantly reduced the inflammatory response and promoted wound healing. These findings show that the study with the title “TREM2 deficiency regulates macrophage apoptosis and repair in radiation-induced skin injury.”
background
Radiation-induced skin injury (RISI) is a common and debilitating complication of radiotherapy, affecting up to 95% of cancer patients undergoing radiotherapy. Persistent inflammation and delayed wound healing remain major clinical challenges, and effective treatment options are limited.
Macrophages play a central role in coordinating inflammatory responses and tissue repair. However, how macrophage fate is regulated under radiation stress is still poorly understood.
Main findings
Using single-cell RNA sequencing, mouse models, and in vitro macrophage assays, researchers identified TREM2 as a key regulator of macrophage survival and repair in RISI.
Radiation induces a distinct TREM2+ macrophage subset that functions as a central hub of the inflammatory signaling network. trem 2 After radiation, transcription is upregulated and radiation-induced oxidative stress reduces TREM2 protein levels. Mechanistically, radiation activates the ROS-NRF2-ADAM17 axis, promoting TREM2 shedding and release of soluble TREM2.
TREM2 deficiency exacerbates macrophage apoptosis, maintains proinflammatory polarization, and delays wound healing. TREM2 confers radioprotection by activating ERK signaling, maintaining mitochondrial integrity, and suppressing caspase-dependent apoptosis. Local delivery of TREM2+ macrophages significantly accelerates wound repair in irradiated skin.
significance
This study identified a previously unrecognized regulatory cascade. This means that “ROS-NRF2-ADAM17-TREM2-ERK” controls the fate of macrophages under radiation stress. The results of this study provide insight into the mechanisms of immune dysfunction in radiation injury and highlight TREM2 as a promising therapeutic target.
Future prospects
Targeting TREM2 signaling or recruiting TREM2+ macrophages may represent new strategies for the treatment of radiation-induced skin damage, improving radiation therapy resistance, and advancing regenerative medicine approaches to radiation injury.
sauce:
Science and Technology Review Publishing
Reference magazines:
Chen, Z. Others. (2025). TREM2 deficiency controls macrophage apoptosis and repair in radiation-induced skin injury. the study. DOI: 10.34133/research.1018. https://spj.science.org/doi/10.34133/research.1018
