tetano
Editor, Senior Moderator
Commun Biol
. 2022 May 4;5(1):415.
doi: 10.1038/s42003-022-03367-z.
IL-25 blockade augments antiviral immunity during respiratory virus infection
Teresa C Williams[SUP] 1 [/SUP], Su-Ling Loo[SUP] 1 [/SUP], Kristy S Nichol[SUP] 1 [/SUP], Andrew T Reid[SUP] 1 [/SUP], Punnam C Veerati[SUP] 1 [/SUP], Camille Esneau[SUP] 1 [/SUP], Peter A B Wark[SUP] 1 2 [/SUP], Christopher L Grainge[SUP] 1 2 [/SUP], Darryl A Knight[SUP] 1 3 4 [/SUP], Thomas Vincent[SUP] 5 [/SUP], Crystal L Jackson[SUP] 5 [/SUP], Kirby Alton[SUP] 5 [/SUP], Richard A Shimkets[SUP] 5 [/SUP], Jason L Girkin[SUP] 1 [/SUP], Nathan W Bartlett[SUP] 6 [/SUP]
Affiliations
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.
. 2022 May 4;5(1):415.
doi: 10.1038/s42003-022-03367-z.
IL-25 blockade augments antiviral immunity during respiratory virus infection
Teresa C Williams[SUP] 1 [/SUP], Su-Ling Loo[SUP] 1 [/SUP], Kristy S Nichol[SUP] 1 [/SUP], Andrew T Reid[SUP] 1 [/SUP], Punnam C Veerati[SUP] 1 [/SUP], Camille Esneau[SUP] 1 [/SUP], Peter A B Wark[SUP] 1 2 [/SUP], Christopher L Grainge[SUP] 1 2 [/SUP], Darryl A Knight[SUP] 1 3 4 [/SUP], Thomas Vincent[SUP] 5 [/SUP], Crystal L Jackson[SUP] 5 [/SUP], Kirby Alton[SUP] 5 [/SUP], Richard A Shimkets[SUP] 5 [/SUP], Jason L Girkin[SUP] 1 [/SUP], Nathan W Bartlett[SUP] 6 [/SUP]
Affiliations
- PMID: 35508632
- DOI: 10.1038/s42003-022-03367-z
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.