IL-10 Mediates the Anti-allergic Effects of PGD₂ Receptor Antagonism in a Mouse Model of Asthma

Asthma is a chronic disease that affects millions of people worldwide. Eosinophils are granulocytes classically characterized as effector cells of the symptomatology of asthma. On the other hand, important immunomodulatory and even homeostatic functions have also been attributed to eosinophils due to cytokine secretion, such as IL-10. Eosinophils also produce and are activated by prostaglandin D₂, a lipid mediator that activates its specific receptors, named DP1 and DP2. The aim of this study was to evaluate the role of DP2 receptor in regulating the secretion of immunomodulatory molecules in a mouse model of asthma. Balb/c mice were sensitized and challenged for 3 consecutive days with ovalbumin. To study the role of selective activation of the DP2 receptor by endogenous PGD₂ produced during allergic response, mice were treated with the DP2 receptor antagonist, Cay10471. And to study the role of IL-10 in the DP2 antagonism-driven effects, Cay10471 treatment was combined with anti-IL-10 antibody. After the allergic challenge, we observed broncho-alveolar eosinophilia with increased levels of PGD₂; parameters that were not modified by Cay10471 treatment. The treatment induced increased levels of Resolvin D₁, PGE₂ and IL-10 in broncho-alveolar lavage, lung and serum during allergic reaction, significantly, and promoted a beneficial effect on the control of pulmonary allergic inflammation, decreasing classical parameters such as broncho-constriction, mucus production, pulmonary fibrosis and the secretion of mediators such as LTC₄, IL-13 and TGF-β. Furthermore, we found that IL-10 seems to be a key mediator in this beneficial effect, since the animals treated with the combination of Cay10471 and anti-IL-10 did not present the improvement promoted by Cay10471 of the allergic inflammatory parameters studied. We unveiled that DP2 receptor antagonism promotes protection during pulmonary allergic inflammation, by a mechanism that seems to depend in part on IL-10 activity.