Modulation of allergic sensitisation and inflammation by natural and induced regulatory T cells.

Despite the ubiquitous presence of inhaled allergens, only some individuals get sensitized and develop allergic disease, while most remain in a tolerant state. A deficiency in regulatory T (Treg) cells potentially underlies this uncontrolled sensitization to harmless environmental allergens in atopic subjects. The rising incidence of allergic diseases could in this context be explained by environmental influences on Treg activity. Concentrating on clinically relevant allergens, we intend to further define the consequences of such a Treg deficiency in a preclinical murine model. We will use house dust mite allergens for sensitization through the airways and for chronic exposure (using total extracts and recombinant allergens). Transgenic and knock-out animals will enable us to specifically eliminate either natural (thymic) T reg cells or TGF-beta-induced Treg cells. The effects of elimination of natural Treg cells on airway sensitization, as well as the effects of eliminating or blocking induced Treg cells on persisting inflammation will then be studied. We expect that these manipulations will enable us to facilitate allergic sensitization and to set up a chronic asthma model, that will subsequently facilitate elucidation of the role of Th1, Th2 and Th17 cytokines on airway remodeling.

Keywords:G.0560.13

Disciplines:Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences