STING/RANTES signaling in airway epithelial cell is a candidate for the bridge from type 1 inflammation to type 2 inflammation.

<bold>Background:</bold> Asthma development can be triggered to various factors, including viral infections. Several pathogen including RS viruses, Rhinovirus, coronavirus activate stimulators of interferon genes (STING), and a small amount of STING agonist enhances immune response during asthma; however, the mechanism is unclear. We have investigated the role of STING in airway epithelium. <bold>Methods:</bold> Airway epithelial cell STING expression was analyzed using the GEO database. We delivered cyclic GMP-AMP (cGAMP), a STING agonist to mice intranasally, and sorted epithelial cells and performed RNA-seq. Human airway epithelial cells (HBEpCs) were stimulated using cGAMP in vitro, then analyzed epithelial cytokines. Next, cGAMP or RANTES with HDM, Der p1, were administrated on Day 1, and challenged with HDM on Day 7, and on Day 8, analyzed cytokine/chemokine levels, bronchoalveolar lavage cell fraction, histology, and the number of group 2 innate lymphoid cells (ILC2s) and dendritic cells (DCs). Furthermore, we have developed RANTES-knockout mouse by CRISPR-Cas9, then analyzed lung inflammation. <bold>Results:</bold> TMEM173, encoding STING, was the most highly expressed in human airway epithelial cells among pattern recognition receptors, and RANTES expression was remarkably upregulated in cGAMP-treated mice and HBEpCs. RANTES, not IL-33 or TSLP, was also activated by cGAMP in HBEpCs. cDC2 was mobilized in cGAMP+HDM and RANTES+HDM administrated lung. RANTES-KO mice showed few eosinophilic inflammation and goblet cell hyperplasia. <bold>Conclusion:</bold> STING/RANTES axis in airway epithelial cell might be a candidate for crucial pathway for connecting type 1 and type 2 inflammation.