Bystander immunotherapy as a strategy to control allergen-driven airway inflammation

Navarro, S., Lazzari, A., Kanda, A., Fleury, S., Dombrowicz, D., Glaichenhaus, N., and Julia, V. (2015) Bystander immunotherapy as a strategy to control allergen-driven airway inflammation. Mucosal Immunology, 8 (4). pp. 841-851.

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Allergic asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR), lung infiltration of Th2 cells, and high levels of IgE. To date, allergen-specific immunotherapy (SIT) is the only treatment that effectively alleviates clinical symptoms and has a long-term effect after termination. Unfortunately, SIT is unsuitable for plurisensitized patients, and highly immunogenic allergens cannot be used. To overcome these hurdles, we sought to induce regulatory CD4+ T cells (Treg) specific to an exogenous antigen that could be later activated as needed in vivo to control allergic responses. We have established an experimental approach in which mice tolerized to ovalbumin (OVA) were sensitized to the Leishmania homolog of receptors for activated c kinase (LACK) antigen, and subsequently challenged with aerosols of LACK alone or LACK and OVA together. Upon OVA administration, AHR and allergic airway responses were strongly reduced. OVA-induced suppression was mediated by CD25+ Treg, required CTLA-4 and ICOS signaling and resulted in decreased numbers of migrating airway dendritic cells leading to a strong impairment in the proliferation of allergen-specific Th2 cells. Therefore, inducing Treg specific to a therapeutic antigen that could be further activated in vivo may represent a safe and novel curative approach for allergic asthma.

Item ID: 36666
Item Type: Article (Research - C1)
ISSN: 1935-3456
Funders: Fondation pour la Recherche Médicale, INSERM
Date Deposited: 18 Mar 2015 04:12
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110203 Respiratory Diseases @ 30%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110701 Allergy @ 60%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 10%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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