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

哮喘是一种炎症性疾病，可以通过接触过敏原而引发。在英国，超过500万人正在接受这种慢性疾病的治疗。过敏原可通过多种机制导致肺部炎症，其中肥大细胞脱颗粒和T细胞分泌细胞因子是两个重要的原因。肥大细胞是最先与吸入的过敏原接触的细胞之一，在那里它们释放出组胺和其他炎症化学物质。树突状细胞通过向T细胞呈递抗原，引导T细胞对抗原作出反应，从而弥合先天免疫和适应性免疫之间的差距。肺内的先天免疫蛋白，包括表面活性剂蛋白A和D （SP-A和SP-D）已被发现对气道适应性免疫反应具有调节作用，并且在先天反应中具有重要作用。具体而言，SP-D已被发现可以减少过敏原诱导的肥大细胞脱颗粒，并可以抑制t细胞的增殖。本项目将利用各种已知过敏原、天然蛋白和重组蛋白的体外细胞培养模型，研究先天免疫蛋白在这些疾病中肺部的免疫调节作用。了解这些蛋白质在肺部过敏反应中的作用，为进一步研究SP-A和SP-D（其天然或重组形式）或其他被研究的蛋白质是否有可能进一步开发成一种新的治疗肺部过敏性炎症的药物提供了基础。

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.