A number of human chronic inflammatory diseases caused by infection, autoimmunity and allergy are strongly linked to B cells that infiltrate the skin, yet the precise role of skin-associated B cells in disease pathogenesis remains unclear. In particular, the underlying mechanisms by which skin exposure to allergens leads to the development and maintenance of IgE production has not been investigated, and a direct contribution by disease-specific B cells to inflammation and allergic reactions in tissue sites such as skin remains to be fully explored. In the studies proposed here we will characterize an expanded population of B cells found in skin of patients with food allergy to red meat and in a novel mouse model of meat allergy our lab recently developed. We will explore the kinetics and phenotype of CCR6hi B cells that accumulate in inflamed skin, evaluate the specific contribution of CCR6hi B cells to disease as well as their function as allergen-specific IgE-producing cells. These efforts will provide a broad assessment of the features and potential functions of this highly expanded B cell population in human allergy.
Skin barrier dysfunction and inflammation are strongly linked with food allergies. In particular, food allergies are associated with B cells that infiltrate the skin, yet the precise role of these skin-associated B cells in disease pathogenesis remains unclear. Food allergies are a growing national public health concern and carry a high risk of life-threatening allergic reactions. There is no treatment to prevent or cure food allergies. Thus, understanding the immune mechanisms that cause sensitization to foods is essential for identifying new treatment strategies that can be used to stop allergic reactions. This proposal explores the immune mechanisms by which skin-associated B cells lead to sensitization and the development of food allergy to red meat. The outcomes from these studies will yield novel mechanistic insights that can inform our thinking of new ways to design effective therapies for the treatment of food allergies.
