Systemic IL-2/anti-IL-2Ab complex combined with sublingual immunotherapy suppresses experimental food allergy in mice through induction of mucosal regulatory T cells

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 administ...

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Detalles Bibliográficos
Autores principales: Smaldini, Paola Lorena, Trejo, Fernando Miguel, Cohen, José L., Piaggio, Eliane, Docena, Guillermo Horacio
Formato: Articulo Preprint
Lenguaje:Inglés
Publicado: 2018
Materias:
Medicina
Food-allergy
Il-2
Sublingual-immunotherapy
Treg
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/99662
https://ri.conicet.gov.ar/11336/86559
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-99662
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Medicina
Food-allergy
Il-2
Sublingual-immunotherapy
Treg
spellingShingle Medicina
Food-allergy
Il-2
Sublingual-immunotherapy
Treg
Smaldini, Paola Lorena
Trejo, Fernando Miguel
Cohen, José L.
Piaggio, Eliane
Docena, Guillermo Horacio
Systemic IL-2/anti-IL-2Ab complex combined with sublingual immunotherapy suppresses experimental food allergy in mice through induction of mucosal regulatory T cells
topic_facet Medicina
Food-allergy
Il-2
Sublingual-immunotherapy
Treg
description 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
format Articulo
Preprint
author Smaldini, Paola Lorena
Trejo, Fernando Miguel
Cohen, José L.
Piaggio, Eliane
Docena, Guillermo Horacio
author_facet Smaldini, Paola Lorena
Trejo, Fernando Miguel
Cohen, José L.
Piaggio, Eliane
Docena, Guillermo Horacio
author_sort Smaldini, Paola Lorena
title Systemic IL-2/anti-IL-2Ab complex combined with sublingual immunotherapy suppresses experimental food allergy in mice through induction of mucosal regulatory T cells
title_short Systemic IL-2/anti-IL-2Ab complex combined with sublingual immunotherapy suppresses experimental food allergy in mice through induction of mucosal regulatory T cells
title_full Systemic IL-2/anti-IL-2Ab complex combined with sublingual immunotherapy suppresses experimental food allergy in mice through induction of mucosal regulatory T cells
title_fullStr Systemic IL-2/anti-IL-2Ab complex combined with sublingual immunotherapy suppresses experimental food allergy in mice through induction of mucosal regulatory T cells
title_full_unstemmed Systemic IL-2/anti-IL-2Ab complex combined with sublingual immunotherapy suppresses experimental food allergy in mice through induction of mucosal regulatory T cells
title_sort systemic il-2/anti-il-2ab complex combined with sublingual immunotherapy suppresses experimental food allergy in mice through induction of mucosal regulatory t cells
publishDate 2018
url http://sedici.unlp.edu.ar/handle/10915/99662
https://ri.conicet.gov.ar/11336/86559
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