CONICET | Buscador de Institutos y Recursos Humanos

Food allergy is an immune-mediated adverse reaction to food and its prevalence has increased worldwide. Defects in Treg cells have been reported in patients with food allergies, suggesting that an impaired tolerance may play a key role in the intestinal allergic inflammation. We aimed to assess the suppressive effect of regulatory T cells to alleviate food allergy in a mouse model. Balb/c mice were orally given CMP (CMPprev) prior to oral sensitization with CMP and cholera toxin (prevention), or after sensitization (desensitization) (CMPdes). Mice were orally challenged with CMP and the immune response was evaluated with in vivo (clinical score and cutaneous tests) and in vitro assays (serum specific IgE, IgG1, IgG2a; IL-5, IL-13, IFN-γ, IL-10 and TGF-β secretion by spleen cells, and analysis of Treg cells in the intestinal mucosa). In vitro and in vivo induced-Treg cells were intravenously transferred to naïve mice before sensitization. We found that symptoms were controlled with oral administration of CMP, with a concomitant negative skin test. Accordingly, serum specific IgE and IgG1 were abrogated (IgE: 1,57±0,2 vs 0,87±0.2 CMPdes; 0,52±0,1 CMPprev), and a substantial reduction in the secretion of IL-5 and IL-13 by stimulated spleen cells from sensitized mice was observed. Importantly, we found that IL-10 and TGF-β were induced with treatment along with an induction of CD4+CD25+FoxP3+ cells (1,02±0,3% vs 10,5±0,5% CMPdes; 4,30±0,2% CMPprev) and IL-10- and TGF-β-producing regulatory T cells (Tregs) in the lamina propria and in MLN. Mice that received Treg by adoptive transfer showed alleviated clinical signs, low levels of serum IgE and induced a negative skin test. We concluded that the oral administration of milk proteins pre- or post-sensitization with CMP induced lamina propria Treg, that restored tolerance and subsequently controlled the allergic response.