放射性炎症是放疗及放射损伤的常见并发症和病人致死的重要因素。细胞质内过度积累的dsDNA可以激活cGAS-STING途径或其它固有免疫途径，最终导致严重的炎症反应。但是电离辐射后调节dsDNA积累的分子及它们介导的放射性炎症的机制尚不明确。申请人前期通过线虫全基因组RNAi文库筛选发现cri-3在电离辐射免疫响应中至关重要，该基因在人和小鼠的同源基因gC1qR敲除后细胞因子的表达及细胞质内dsDNA含量均大幅减少，进一步研究发现gC1qR与MRE11核酸酶结合抑制后者对dsDNA的降解。故我们提出gC1qR通过调节MRE11核酸酶的活性去调节dsDNA含量，进而通过cGAS-STING途径促进电离辐射炎症反应的科学假说。申请人拟通过建立细胞和小鼠的放射性炎症模型，探究gC1qR在细胞因子表达和放射性炎症中的作用，为临床放射性炎症的机理提供新的理论依据，并为防治放射性炎症探索潜在的干预靶点。

Radiation-induced inflammation is a common complication of radiotherapy and radiation injury and an important factor in the death of patients. Excessive accumulation of dsDNA in the cytoplasm can activate the cGAS-STING pathway or other innate immune pathways, ultimately leading to severe inflammatory responses. However, the mechanisms involved in the regulation of dsDNA accumulation in cells and the mechanisms by which they mediate radiation-induced inflammation after ionizing radiation are unclear. In preliminary experiment, the applicants screened the nematode genome-wide RNAi library and found that cri-3 was crucial in the immune response of ionizing radiation. The expression of cytokines and dsDNA content in the cytoplasm were significantly decreased after knockout of human and mouse homolog gC1qR. Further studies found that gC1qR binds to MRE11 and inhibits the degradation of dsDNA by the latter. Therefore, we propose a scientific hypothesis that gC1qR regulates the dsDNA content by regulating the activity of MRE11 nuclease, and then promotes the inflammatory response of ionizing radiation through the cGAS-STING pathway. Applicants intend to explore the mechanism of gC1qR-mediated ionizing radiation leading to expression of cytokines and its role in radiation-induced inflammation by establishing a model of radiation-induced inflammation in cells and mice, providing a new theoretical basis for the mechanism of clinical radiation-induced inflammation, and exploring potential targets for potential intervention target in the prevention and treatment of radiation-induced inflammation.