Notch signaling contributes to the establishment of sustained unresponsiveness to food allergens by oral immunotherapy

BackgroundOral immunotherapy (OIT) aims to establish desensitization and sustained unresponsiveness (SU) in patients with food allergy by ingestion of gradually increasing doses specific allergens. However, little is known about the mechanisms which OIT induces SU allergens.ObjectivesWe investigated role Notch signaling, controls cell fate decisions many types immune cells induction treatment.MethodsTwo mouse models, ovalbumin-induced OIT, were generated. To elucidate signaling OIT-induced SU, mice intraperitoneally injected inhibitor N-[(3,5-difluorophenyl)acetyl]-l-alanyl-2-phenylglycine-1,1-dimethylethyl ester during treatment period.ResultsOvalbumin-sensitized desensitized also had induced treatment, whereas repeated challenges ovalbumin caused development severe allergic reactions ovalbumin-sensitized mice. Administration period inhibited establishment but did not affect desensitization. a systemic expansion IL-10–producing CD4+ T cells, including TH2 myeloid-derived suppressor (MDSCs), particularly monocytic MDSC subpopulation. Inhibition prevented those cells. In vitro cultures bone marrow showed that directly promoted generation MDSCs. addition, contribution MDSCs was confirmed depletion anti-Gr1 antibody.ConclusionNotch contributes through immunosuppressive such as Oral We treatment. Two period. Ovalbumin-sensitized antibody.