Prostaglandin D2 is a lipid mediator generated from the metabolism of arachidonic acid. We recently discovered (Werder et al, Science Translational Medicine) that PGD2 can enhance or suppress the production of type III IFN, a potent antiviral cytokine. This contrasting effect is dependent on the receptor subtype that is activated. In both COPD and asthma, acute exacerbations (or ‘attacks’) are associated with a respiratory infection, and in the setting of a viral infection, this has been associated with impaired production of type I and III IFNs. Here we will investigate in clinical samples and in a preclinical model of COPD, whether PGD2 levels are elevated and whether this mediator contributes to the loss in viral control. We will also explore the molecular mechanism by which DP1 agonism promotes the production of innate IFNs.