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IL-25 blockade augments antiviral immunity during respiratory virus infection

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posted on 2025-05-09, 01:42 authored by Teresa C. Williams, Su Ling LooSu Ling Loo, Crystal L. Jackson, Kirby Alton, Richard A. Shimkets, Jason GirkinJason Girkin, Nathan BartlettNathan Bartlett, Kristy NicholKristy Nichol, Andrew ReidAndrew Reid, Punnam Chander VeeratiPunnam Chander Veerati, Camille EsneauCamille Esneau, Peter WarkPeter Wark, Christopher GraingeChristopher Grainge, Darryl A. Knight, Thomas Vincent
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.

History

Journal title

Communications Biology

Volume

5

Article number

415

Publisher

Nature Publishing Group

Language

  • en, English

College/Research Centre

College of Health, Medicine and Wellbeing

School

School of Biomedical Sciences and Pharmacy

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This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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