Mechanisms underlying airway sensitisation and tolerance towards major allergens of Dermatophagoides mites.

Several data suggest that a deficiency in regulatory T (Treg) cells underlies the loss of tolerance and uncontrolled sensitization to harmless environmental (food and inhaled) allergens in atopic subjects. Concentrating on clinically relevant recombinant allergens from a major allergen source, house dust mites (HDM), we intend to further document and define this deficiency as well as its consequences, and to find new original approaches to restoration of tolerance, both with the aim to develop new approaches to prevention and treatment. To this end, a preclinical murine model of respiratory allergy will be exploited for mechanistic studies on immunologic and inflammatory events in HDM induced airway disease. Moreover, we are in the process of constructing a transgenic mouse strain with a TCR specific for a peptide of der p 2. The abundant presence of allergen-specific T cells makes such a TCR transgene a useful tool for studying various aspects of the sensitization and T cell differentiation process, in particular the induction and activity of Treg cells; to evaluate environmental factors that promote (or protect from) sensitization, and to elaborate novel therapeutic approaches for tolerance induction. In parallel, we will study effects of HDM allergens on human innate immune cells, in particular on dendritic cells and epithelial cells, as well as on peripheral T cell subsets, with the aim to translate the murine findings into the human situation of allergic disease.....

Keywords:Airway inflammation, Regulatory T cells, Tolerance, Interleukin-17, Cytokines, Eosinophils, House dust mite, Respiratory allergy

Disciplines:Respiratory medicine, Immunology