CONICET | Buscador de Institutos y Recursos Humanos

Food allergy is a worldwide immune-mediated adverse reaction to food and is a growing clinical concern. Sublingual allergen immunotherapy has been proposed as an alternative therapy and there is so far no standardized and approved procedure. In this work, we aimed to induce oral tolerance to cow`s milk protein (CMP) through the sublingual administration of milk proteins. Balb/c mice were intragastrically sensitized with CMP plus cholera toxin. Then sensitized mice underwent sublingual immunotherapy (SLIT) once a week during eight weeks with CMP (CMPdes). Finally, mice were orally challenged and the SLIT efficacy was evaluated with in vivo (clinical score and cutaneous test) and in vitro assays (serum specific antibodies by ELISA, IL-5, IL-13, IL-25, TSLP, IL-10 and TGF-β by ELISA or qPCR in splenocytes, intestinal and sublingual mucosa). Cell infiltrate was analyzed by histology and Tregs were evaluated by flow cytometry. Mice sensitized to CMP exhibited hypersensitivity symptoms, high levels of specific IgE, positive cutaneous test, cell infiltrate in gut and a CMP-specific Th2 biased response. SLIT with CMP (10 ng/dose) produced a significant reduction of the clinical score after the oral challenge, negativized the cutaneous test, suppressed the production of specific-IgE (1,57±0,2 vs 0,61±0.1 CMPdes), rendered a lower secretion of cytokines (IL-5 and IL-13). Treated mice showed an increase of mucosal IL-10 and TGF-β (34,2±8,3 vs 138,0±12,7 pg/200mg gut CMPdes; p<0.001), . Besides, we found high levels of IL-10, IFN-γ, IL-25 and TSLP in the sublingual mucosa and CD4+CD25+Foxp3+ Tregs. We demonstrated in a murine model of milk allergy that SLIT down-modulated the mucosal and systemic allergic immune response in sensitized mice through the induction of specific tolerance