| Title | IL-25 blockade augments antiviral immunity during respiratory virus infection. | ||
| Author | Williams, Teresa C; Loo, Su-Ling; Nichol, Kristy S; Reid, Andrew T; Veerati, Punnam C; Esneau, Camille; Wark, Peter A B; Grainge, Christopher L; Knight, Darryl A; Vincent, Thomas; Jackson, Crystal L; Alton, Kirby; Shimkets, Richard A; Girkin, Jason L; Bartlett, Nathan W | ||
| Journal | Commun Biol | Publication Year/Month | 2022-May |
| PMID | 35508632 | PMCID | PMC9068710 |
| Affiliation + expend | 1.The University of Newcastle and Hunter Medical Research Institute, Newcastle, NSW, Australia. | ||
IL-25 is implicated in the pathogenesis of viral asthma exacerbations. However, the effect of IL-25 on antiviral immunity has yet to be elucidated. We observed abundant expression and colocalization of IL-25 and IL-25 receptor at the apical surface of uninfected airway epithelial cells and rhinovirus infection increased IL-25 expression. Analysis of immune transcriptome of rhinovirus-infected differentiated asthmatic bronchial epithelial cells (BECs) treated with an anti-IL-25 monoclonal antibody (LNR125) revealed a re-calibrated response defined by increased type I/III IFN and reduced expression of type-2 immune genes CCL26, IL1RL1 and IL-25 receptor. LNR125 treatment also increased type I/III IFN expression by coronavirus infected BECs. Exogenous IL-25 treatment increased viral load with suppressed innate immunity. In vivo LNR125 treatment reduced IL-25/type 2 cytokine expression and increased IFN-beta expression and reduced lung viral load. We define a new immune-regulatory role for IL-25 that directly inhibits virus induced airway epithelial cell innate anti-viral immunity.