HMGB1 recruits NK cells by CXCL12/CXCR4 axis contributing to persistent airway inflammation and AHR during the later stage of RSV infection

Abstract Our previous studies have shown that both high-mobility group box-1 (HMGB1) and natural killer cells (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 receptor chemokine receptor 4 (CXCR4) were reported to play important roles in recruitment of immune cells. The relationships between them were unclear. We investigated whether HMGB1 can recruit NK cells by CXCL12/CXCR4 axis, thereby mediating RSV induced persistent airway disorders. Anti-HMGB1 neutralizing antibody and inhibitor of CXCR4 (AMD3100) were administered to observe the change of the percentage of NK cells and the airway disorders in nude mice. In the study, we found that mRNA and protein expression of HMGB1 were elevated in the later stage of RSV infection and persistent airway inflammation and AHR were diminished after administration of anti-HMGB1 antibodies with NK cells decreased significantly. At the same time, CXCL12 and CXCR4 were reduced after HMGB1 blockade. Treatment with AMD3100 was found to significantly suppress the recruitment of NK cells and alleviate the airway disorders. Therefore, HMGB1 recruits NK cells by CXCL12/CXCR4 axis contributing to persistent airway inflammation and AHR during the later stage of RSV infection.