CONICET | Buscador de Institutos y Recursos Humanos

Food allergy is an immunological disorder caused by a breakdown in immunologic tolerance. Treatment consists of strict avoidance of food allergens. However, corrective therapies are being studied. We aimed to induce oral tolerance to cow`s milk proteins (CMP) using CMP in an IgE-mediated food allergy mouse model. Balb/c mice were intragastrically given CMP prior to (CMPprev)or after (CMPdes)sensitization with CMP plus cholera toxin. Mice were orally challenged with CMP and the immune response was evaluated with in vitro (serum IgE, IgG1, IgG2a; TNF-α, IL-6, IL-17A, IL-5, IL-13, IFN-γ, IL-10 and TGF-β expression ?qPCR- andproduction ?ELISA or flow citometry-by spleen cells and intestinal mucosa) and in vivo assays (clinical score and cutaneous tests).Histology was analyzed in gut specimens to evaluate the inflammatory infiltrate. We found a lower mean clinical score in CMPprev and CMPdes mice after the oral challenge with CMP, as compared to sensitized mice, with a negativization of skin tests in tolerized mice. Immunological changes included decreased serum specific IgE (1,57±0,2 vs 0,87±0.2 CMPdes;0,52±0,1 CMPprev) and IgG1(2,07±0,7 vs 0,91±0,2 CMPdes; 0,11±0,05 CMPprev), decreased protein and mRNA level of IL-6, IL-5 and IL-13 (p<0,05), and induction of regulatory Tcells in duodenum of treated mice (0,73±0,01% vs 1,055±0,01% CMPdes; and vs 11,10±1,6% CMPprev) and in mesenteric lymph nodes (0,373±0,3% vs 2,675±1,1% CMPprev) in tolerized mice. TGF-β and IL-10 were induced in lamina propria and we found increased intestinal CD4+ CD25+ FoxP3+ cells as source of TGF-β and IL-10. Besides, a mild inflammatory infiltrate of mononuclear cells was observed in duodenum of sensitized mice, but not in treated mice. Oral immunotherapy with milk proteins down-modulated the allergic specific immune response in CMP-sensitized mice.This approach could provide a new therapeutic anti-inflammatory intervention for CMP food allergy, either for prevention or desensitization