IL-25 blockade augments antiviral immunity during respiratory virus infection

• DOI: 10.1038/s42003-022-03367-z
• Publication Date: 2022-05-04T10:04:21Z
• Authors: Teresa C. Williams; Su-Ling Loo; Kristy S. Nichol; Andrew T. Reid; Punnam C. Veerati; Camille Esneau; Peter A. B. Wark; Christopher L. Gr...; Darryl A. Knight; Thomas Vincent; Crystal L. Jackson; Kirby Alton; Richard A. Shimkets; Jason L. Girkin; Nathan W. Bartlett
• Keywords: 0301 basic medicine; 0303 health sciences; Rhinovirus; QH301-705.5; Interleukin-17; Sustainable Development Goals; asthma; bronchial epithelial cells (BECs); Antiviral Agents; Article; Asthma; Immunity, Innate; antiviral immunity; 3. Good health; 03 medical and health sciences; IL-25; rhinovirus; Virus Diseases; Humans; Biology (General); innate immunity; SDG 3

AbstractIL-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.