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- Title
IL-25 blockade augments antiviral immunity during respiratory virus infection.
- Authors
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.
- Abstract
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-β 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. IL-25 and its receptor are expressed in airway epithelial cells of healthy individuals and patients with asthma and antibody-mediated blockade of IL-25 enhances antiviral immunity and blocks virus-exacerbated asthma responses.
- Subjects
VIRUS diseases; EPITHELIAL cells; NATURAL immunity; IMMUNITY; BLOCKADE
- Publication
Communications Biology, 2022, Vol 5, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-022-03367-z