Transient Suppression and Functional Modulation of Mucosal Mast Cells for the Treatment of Allergic Disease

Abstract Food allergy is estimated to affect about 5 percent in children and adults and causes life-threatening reactions. Especially food allergy in infant and child shows severe gastrointestinal symptoms, including diarrhea, vomiting, and abdominal pain. To control the food allergy, allergen desensitization by oral immunotherapy (OIT), has been shown to an effective therapeutic approach; however, limited information is currently available for basic understandings of OIT induced immunological events at intestinal mucosa. In this study, we found that orally desensitized intestinal mast cells acquired the regulatory function for the inhibition of food allergic response. Indeed, the gene analysis showed the increase of regulatory cytokine IL-2 and IL-10 expressions in orally-desensitized intestinal mast cells; on the contrary, decreased Th2 cytokine expressions were suppressed by epigenetic control. Thereby, mice depleting these regulatory mast cells during OIT led to the reduction of functional regulatory T cell-mediated inhibition of allergic responses. These findings newly uncovered characteristics desensitized mast cells to acquire regulatory suppressive milieu in the allergic disease mucosa and indicated the novel roles of mast cells in the effective anti-allergic therapy.