CXCL12/CXCR4 axis is involved in the recruitment of NK cells by HMGB1 contributing to persistent airway inflammation and AHR during the late stage of RSV infection
CXCL12/CXCR4 axis is involved in the recruitment of NK cells by HMGB1 contributing to persistent airway inflammation and AHR during the late stage of RSV infection
复制标题
CXCL12/CXCR4 轴参与 HMGB1 招募 NK 细胞，导致 RSV 感染后期持续气道炎症和 AHR
DOI：
10.1007/s12275-023-00018-8
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发表时间：
--
影响因子：
3
通讯作者：
Enmei Liu
中科院分区：
文献类型：
--
作者：
Sisi Chen;Wei Tang;Guangyuan Yu;Zhengzhen Tang;Enmei Liu
我们以前的研究表明，高迁移率族蛋白1（HMGB 1）和自然杀伤（NK）细胞有助于呼吸道合胞病毒（RSV）诱导的持续气道炎症和气道高反应性（AHR）。同时，趋化因子配体12（CXCL 12）及其特异性受体（趋化因子受体4，CXCR 4）在免疫细胞的募集中起重要作用。据报道，CXCL 12与HMGB 1形成复合物，结合CXCR 4并增加炎性细胞迁移。RSV感染模型中HMGB 1、NK细胞和趋化因子之间的关系尚不清楚。应用抗HMGB 1中和抗体和CXCR 4抑制剂（AMD 3100），观察裸鼠和BALB/c小鼠NK细胞的变化和气道病变。结果显示，HMGB 1的mRNA和蛋白水平在RSV感染晚期升高，抗HMGB 1抗体治疗后持续性气道炎症和AHR减轻，CXCR 4 +NK细胞显著减少。此外，HMGB 1阻断后CXCL 12和CXCR 4减少。用AMD 3100治疗显著抑制NK细胞的募集并减轻气道障碍。因此，CXCL 12/CXCR 4轴参与HMGB 1募集NK细胞，导致RSV感染晚期持续气道炎症和AHR。
We previously showed that both high-mobility group box-1 (HMGB1) and natural killer (NK) cells contribute to respiratory syncytial virus (RSV)-induced persistent airway inflammation and airway hyperresponsiveness (AHR). Meanwhile, Chemokine (C-X-C motif) ligand 12 (CXCL12) and its specific receptor (chemokine receptor 4, CXCR4) play important roles in recruitment of immune cells. CXCL12 has been reported to form a complex with HMGB1 that binds to CXCR4 and increases inflammatory cell migration. The relationship between HMGB1, NK cells and chemokines in RSV-infected model remains unclear. An anti-HMGB1 neutralizing antibody and inhibitor of CXCR4 (AMD3100) was administered to observe changes of NK cells and airway disorders in nude mice and BALB/c mice. Results showed that the mRNA expression and protein levels of HMGB1 were elevated in late stage of RSV infection and persistent airway inflammation and AHR were diminished after administration of anti-HMGB1 antibodies, with an associated significant decrease in CXCR4+NK cells. In addition, CXCL12 and CXCR4 were reduced after HMGB1 blockade. Treatment with AMD3100 significantly suppressed the recruitment of NK cells and alleviated the airway disorders. Thus, CXCL12/CXCR4 axis is involved in the recruitment of NK cells by HMGB1, contributing to persistent airway inflammation and AHR during the late stage of RSV infection.