Researchers from several Chinese hospitals have published new findings on the role of TREM2 in supporting macrophage survival and aiding skin repair following radiation damage. The study, led by Professor Yiming Zhang of Xinqiao Hospital at Army Medical University, Professor Fazhi Qi of Zhongshan Hospital at Fudan University, and Professor Junli Zhou of the Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), examines how macrophages respond to radiation-induced skin injury.
The research team reports that radiation-induced skin injury is a frequent complication for patients undergoing radiotherapy, affecting up to 95% of those treated for cancer. Persistent inflammation and delayed healing are common problems for these patients, with few effective treatments available.
Macrophages play a key role in managing inflammation and promoting tissue repair after such injuries. However, the regulation of their survival under radiation stress has not been fully understood. Using single-cell RNA sequencing, mouse models, and laboratory assays, the scientists identified TREM2 as a critical factor in macrophage survival and function during radiation-induced skin injury.
According to the researchers, "irradiation activates the ROS-NRF2-ADAM17 axis, which mediates TREM2 shedding, leading to increased macrophage apoptosis and impaired reparative function." They found that while Trem2 gene expression increases after irradiation, actual TREM2 protein levels decrease due to oxidative stress caused by radiation. This process leads to the release of soluble TREM2.
The study further demonstrates that "supplementation with TREM2+ macrophages markedly attenuated inflammatory responses and accelerated wound healing." The authors state: "TREM2 deficiency exacerbates macrophage apoptosis, sustains pro-inflammatory polarization, and delays wound healing. TREM2 confers radioprotection by activating ERK signaling, preserving mitochondrial integrity and suppressing caspase-dependent apoptosis. Local delivery of TREM2+ macrophages significantly accelerates wound repair in irradiated skin."
This research identifies a regulatory cascade—described as "ROS-NRF2-ADAM17-TREM2-ERK"—that controls macrophage fate under conditions of radiation stress. The findings provide insight into immune system dysfunction following radiation exposure and suggest that targeting TREM2 or providing additional TREM2+ macrophages could be potential strategies for treating radiation-induced skin injuries.
The researchers conclude: "Targeting TREM2 signaling or supplementing TREM2+ macrophages may represent novel strategies for treating radiation-induced skin injury, improving radiotherapy tolerance, and advancing regenerative medicine approaches for radiation damage."
