Characterisation of the role of innate immune proteins in inflammatory lung diseases

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Asthma is an inflammatory disease that can be triggered through contact with allergens. In the UK, over five million people are receiving treatment for the chronic disease. Allergens can lead to inflammation of the lungs through multiple mechanisms, with two important causes being degranulation of mast cells, and secretion of cytokines by T cells. Mast cells are among the first cells to come in contact with inhaled allergens, where upon they release histamine and other inflammatory chemicals. Dendritic cells bridge the gap between innate and adaptive immunity by presenting antigens to T cells, priming them to respond to antigens. Innate immune proteins in the lungs, including surfactant proteins A and D (SP-A and SP-D) have been found to have a modulatory effect on the airway adaptive immune response, as well as being important for the innate response. Specifically, SP-D has been found to decrease the allergen-induced degranulation of mast cells and can inhibit the proliferation of T-cells. This project will investigate the immunomodulatory role of innate immune proteins in the lungs in these diseases using various in vitro cell culture models with known allergens and native and recombinant proteins. Understanding the role these proteins play in allergic reactions in the lungs provides a foundation for future work into whether SP-A and SP-D (native or recombinant forms thereof) or other proteins investigated would have a potential to be developed further into a new therapeutic agent against allergic inflammation in the lungs.