Investigating the Systemic Effects of Cat Allergen-Induced Allergic Rhinitis

8.5 million cats live in Canada, approximately in every third household. However, one in five Canadians is allergic to cats, often in combination with other allergic diseases. To date, only symptomatic treatments are available for cat allergies, but no prevention or cure. To improve treatment options for cat-allergic individuals, we need to better understand the mechanisms underlying this common cause of rhinitis. While clinical data provide important insights into immunological phenotypes and symptom severity, preclinical models allow for dissection of the immune response throughout the whole organism, and across a long timespan. Notably, the main effector cells mediating allergic rhinitis –eosinophilic granulocytes– derive from hematopoietic stem cells (HSCs). HSCs reside within bone marrow (BM) –a location far from the nose as primary site of the allergy. Based on previous studies on respiratory infections, we hypothesize that sensitization to cat allergens in the nose initiates HSC activation and expansion in the BM. These HSCs produce eosinophils that are epigenetically programmed for rapid and strong reaction upon allergen encounter, perpetuating allergic sensitization. We have established a preclinical model for cat allergen-induced rhinitis in which wild-type C57BL/6 mice are intranasally exposed to cat dander, mimicking human sensitization. Similar to our clinical study, eosinophils increase in the nasal mucosa upon cat allergen exposure in mice. We are now testing the systemic changes occurring throughout allergic sensitization and challenge. Specifically, we will analyze immune cell and HSC populations in lung, blood, and BM by flow cytometry. We will compare the phenotypes of these cells with effector eosinophils in the nose during allergen exposure. Using mice for the investigation of cat allergy enables us to trace eosinophil migration and systemic distribution of these potent allergy-promoting cells. These insights are fundamental to determining novel intervention foci, and to understanding how cat allergy links with other allergic diseases.