Artículo
Systemic IL-2/anti-IL-2Ab complex combined with sublingual immunotherapy suppresses experimental food allergy in mice through induction of mucosal regulatory T cells
Smaldini, Paola Lorena
; Trejo, Fernando Miguel
; Cohen, José L.; Piaggio, Eliane; Docena, Guillermo H.
Fecha de publicación:
01/2018
Editorial:
Wiley Blackwell Publishing, Inc
Revista:
Allergy
ISSN:
0105-4538
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Therapeutic tolerance restoration has been proven to modify food allergy in patients and animal models and although sublingual immunotherapy (SLIT) has showed promise, combined therapy may be necessary to achieve a strong and long‐term tolerance. In this work, we combined SLIT with systemic administration of IL‐2 associated with an anti‐IL‐2 monoclonal antibody (IL‐2/anti‐IL‐2Ab complex or IL‐2C) to reverse the IgE‐mediated experimental allergy. Balb/c mice were sensitized with cholera toxin and milk proteins and orally challenged with allergen to elicit hypersensitivity reactions. Then, allergic mice were treated with a sublingual administration of very low amounts of milk proteins combined with intraperitoneal injection of low doses of IL‐2C. The animals were next re‐exposed to allergens and mucosal as well as systemic immunological parameters were assessed in vivo and in vitro. The treatment reduced serum specific IgE, IL‐5 secretion by spleen cells and increased IL‐10 and TGF‐β in the lamina propria of buccal and duodenal mucosa. We found an augmented frequency of IL‐10‐secreting CD4+CD25+Foxp3+ regulatory T cells (Treg) in the submaxilar lymph nodes and buccal lamina propria. Tregs were sorted, characterized and adoptively transferred to naïve mice, which were subsequently sensitized. No allergy was experienced in these mice and we encouragingly discovered a faster and more efficient tolerance induction with the combined therapy compared with SLIT. The combination of two therapeutic strategies rendered Treg‐mediated tolerance more efficient compared to individual treatments and reversed the established IgE‐mediated food allergy. This approach highlights the ability of IL‐2C to expand Tregs, and it may represent a promising disease‐modifying therapy for managing food allergy
Palabras clave:
FOOD-ALLERGY
,
IL-2
,
SUBLINGUAL-IMMUNOTHERAPY
,
TREG
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Identificadores
Colecciones
Articulos(CIDCA)
Articulos de CENTRO DE INV EN CRIOTECNOLOGIA DE ALIMENTOS (I)
Articulos de CENTRO DE INV EN CRIOTECNOLOGIA DE ALIMENTOS (I)
Articulos(IIFP)
Articulos de INST. DE ESTUDIOS INMUNOLOGICOS Y FISIOPATOLOGICOS
Articulos de INST. DE ESTUDIOS INMUNOLOGICOS Y FISIOPATOLOGICOS
Citación
Smaldini, Paola Lorena; Trejo, Fernando Miguel; Cohen, José L.; Piaggio, Eliane; Docena, Guillermo H.; Systemic IL-2/anti-IL-2Ab complex combined with sublingual immunotherapy suppresses experimental food allergy in mice through induction of mucosal regulatory T cells; Wiley Blackwell Publishing, Inc; Allergy; 73; 1-2018; 885-895
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