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

先天免疫蛋白在炎症性肺部疾病中作用的表征

• 批准号: 2397872
• 金额: --
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2397872
• 关键词: Characterisation; role; innate; immune; proteins

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.

哮喘是一种炎症性疾病，可以通过与过敏原接触而触发。在英国，超过500万人正在接受慢性疾病的治疗。过敏原会通过多种机制导致肺部炎症，这两个重要原因是肥大细胞的脱粒，而T细胞通过T细胞分泌细胞因子。肥大细胞是最早与吸入过敏原接触的细胞之一，在这些细胞中，它们释放组胺和其他炎症化学物质。树突状细胞通过向T细胞展示抗原，启动它们以对抗原反应，弥合先天和适应性免疫之间的差距。肺中的先天免疫蛋白，包括表面活性剂蛋白A和D（SP-A和SP-D），对气道适应性免疫反应具有调节作用，并且对先天反应很重要。具体而言，已经发现SP-D可减少过敏原诱导的肥大细胞脱粒，并可以抑制T细胞的增殖。该项目将使用具有已知过敏原，天然和重组蛋白的各种体外细胞培养模型，研究先天免疫蛋白在肺中的免疫调节作用。了解这些蛋白质在肺中的过敏反应中所起的作用为将来的工作奠定了基础，以实现SP-A和SP-D（本地或重组形式）或所研究的其他蛋白质的作用，将有可能进一步发展为针对肺部过敏性炎症的新治疗剂。

项目成果

Evolutionary remodelling of N-terminal domain loops fine-tunes SARS-CoV-2 spike.

• DOI: 10.15252/embr.202154322
• 发表时间: 2022-10-06
• 期刊: EMBO reports
• 影响因子: 7.7
• 作者: Cantoni D;Murray MJ;Kalemera MD;Dicken SJ;Stejskal L;Brown G;Lytras S;Coey JD;McKenna J;Bridgett S;Simpson D;Fairley D;Thorne LG;Reuschl AK;Forrest C;Ganeshalingham M;Muir L;Palor M;Jarvis L;Willett B;Power UF;McCoy LE;Jolly C;Towers GJ;Doores KJ;Robertson DL;Shepherd AJ;Reeves MB;Bamford CGG;Grove J
• 通讯作者: Grove J