Interleukin-22 downregulates double-stranded RNA-induced expression of B7-H1/PD-L1 on airway epithelial cells

Background and Aim: Airway viral infectionis a cause of exacerbations of COPD. B7-H1/PD-L1is a coinhibitory molecule implicated in an escape mechanism of viruses from the host immune systems. Molecules suppressing expression of B7-H1/PD-L1 may be preventive for virus-induced exacerbation. Interleukin-22 (IL-22) is a member of the IL-10 family that is produced from a variety of immune cells and has protective properties on tissue-structural cells including epithelial cells. We investigated the effect of IL-22 on the expression of B7-H1/PD-L1. Methods: Airway epithelial cell lines were treated with or without an analog of viral double-stranded RNA, polyinosinic-polycytidylic acid (poly I:C) in the presence or absence of human IL-22. The expression of B7-H1/PD-L1 was assessed by flow cytometry. Results: The expression of B7-H1/PD-L1 was upregulated by poly I:C in a dose-dependent manner. The magnitude of B7-H1/PD-L1 expression remained constant from 24h to 48h after the stimulation of poly I:C. Without poly I:C, the expression of B7-H1/PD-L1 was not affected by treatment with IL-22. Poly I:C-induced upregultaion of B7-H1/PD-L1 was significantly attenuated by treatment with IL-22. Conclusion: IL-22 downregluates double-stranded RNA-induced expression of B7-H1/PD-L1 on airway epithelial cells, suggesting a beneficial role of IL-22 in virus-associated pathogenesis of COPD. The examinations for in vivo effect of IL-22 is underway using a murine model of poly I:C-induced inflammation.