Chen Cheng, Cai Xin, Liu Zhihui, Zhang Weiguang, Yang Jiacai, Tang Yuanyang, Chen Yunxia, Huang Yong, Hu Wengang, Zhang Xiaorong, Zhou Junyi, Wu Yanjun, Yin Wenjing, Shang Ruoyu, Lu Qudong, Sheng Hao, Ju Zhenyu, Luo Gaoxing, He Weifeng
State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Medical University), 30 Gaotanyan Main Street, Shapingba District, Chongqing 400038, China.
Chongqing Key Laboratory for Disease Proteomics, 30 Gaotanyan Main Street, Shapingba District, Chongqing 400038, China.
J Leukoc Biol. 2025 Mar 14;117(3). doi: 10.1093/jleuko/qiae175.
Efficient cutaneous wound healing requires a coordinated transition between inflammatory phases mediated by dynamic changes in leukocyte subset populations. Here, we identify STING as a key innate immune mediator governing timely resolution of inflammation by regulating macrophage dynamics during skin repair. Using a mouse model, we show STING deficiency caused delayed wound closure associated with abnormal persistence of TNF-α+ leukocytes. This resulted from the impaired macrophage recruitment. STING controlled the trafficking of bone marrow myeloid cells into blood and wounds, intrinsically enhancing macrophage migratory capacity through STAT3 activation. Specifically, STING modulated the production of monocyte chemokines and their receptors CCR2/CCR5 to enable efficient egress and wound infiltration. Consequently, disrupted systemic and local STING-STAT3-chemokine signaling combine to delay macrophage influx. This study elucidates STING as a critical rheostat tuning macrophage responses through STAT3 to orchestrate inflammatory resolution necessary for efficient wound healing. Our findings have broad implications for targeting STING therapeutically in both regenerative medicine and inflammatory disease contexts.
高效的皮肤伤口愈合需要在由白细胞亚群动态变化介导的炎症阶段之间进行协调过渡。在这里，我们确定了干扰素基因刺激蛋白（STING）是一种关键的固有免疫介质，它通过在皮肤修复过程中调节巨噬细胞动态来控制炎症的及时消退。使用小鼠模型，我们发现STING缺陷导致伤口愈合延迟，这与TNF-α+白细胞的异常持续存在有关。这是由于巨噬细胞募集受损所致。STING控制骨髓髓样细胞进入血液和伤口的运输，通过激活STAT3内在地增强巨噬细胞的迁移能力。具体而言，STING调节单核细胞趋化因子及其受体CCR2/CCR5的产生，以实现有效的流出和伤口浸润。因此，系统性和局部STING-STAT3-趋化因子信号的破坏共同导致巨噬细胞流入延迟。这项研究阐明了STING作为一种关键的调节因子，通过STAT3调节巨噬细胞反应，以协调有效伤口愈合所需的炎症消退。我们的发现对于在再生医学和炎症性疾病背景下以STING为治疗靶点具有广泛的意义。
