TNF-related apoptosis-inducing ligand (TRAIL) mediates the resolution of allergic airway inflammation induced by chronic allergen inhalation

• Grant number: 14/05707-8
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Duration: April 01, 2014 - September 30, 2014
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Momtchilo Russo
• Grantee: Momtchilo Russo
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Allergic asthma can vanish over time either spontaneously or induced by allergen specific immunotherapy. In mice with established airway allergic inflammation, chronic intranasal allergen challenges decreases progressively airway allergic inflammation. Here we compared the contribution of different regulatory pathways that could be associated with this phenomenon, known as local inhalational tolerance. We found that inhalational tolerance was not associated with increased number of regulatory T cells or suppressive cytokines. Instead, it was associated with increased apoptosis of airway inflammatory leukocytes revealed by annexin-V staining and the expression of apical caspase 8 and effector caspase 3. Also, the transition from acute to chronic phase was associated with a shift in the expression of pro-allergic to pro-apoptotic molecules. The TNF-related apoptosis-inducing ligand (TRAIL) was found to be a key molecule in mediating resolution of allergic inflammation because anti-TRAIL treatment blocked apoptosis and increased the infiltration of Th2 cells and eosinophils. Notably, repeated intranasal treatment with recombinant TRAIL in established airway allergic inflammation, augmented leukocyte apoptosis and decreased the frequency of IL-5-producing Th2 cells and eosinophils to airways. Our data indicate that TRAIL signaling is sufficient for down modulation of allergic airway disease suggesting a potential therapeutic use of TRAIL for asthma treatment. (AU)