The role of CRTH2 + CD8 + T cells in severe asthma

CRTH2 CD8 T 细胞在严重哮喘中的作用

• 批准号: 1946480
• 金额: --
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1946480
• 关键词: role; CRTH2; CD8; cells; severe

Keywords: Immunology & Infectious diseaseThe immune responses causing severe asthma have been defined as possessing a ""type 2"" cytokine bias. These cytokines, which include interleukins 4, 5,and 13 are secreted by lymphoid subsets and attract the classic eosinophilic infiltrates associated with the disease. We have recently found that in human disease a potent source of these cytokines in the lung is the CD8+ T cell compartment. CD8+ T cells which secrete type 2 cytokines express the molecule CRTH2, a functional receptor for PGD2 (prostaglandin D2) and are the most enriched in disease, including in the lung. This is a surprising and novel result (manuscript in preparation) and suggests they may play a critical role in disease pathogenesis. Using samples obtained from patients with severe asthma and controls, this project will address: The full functional capacity of Tc2 cells in response to distinct stimuli The functional interactions of Tc2 cells with epithelial cells and eosinophils and their localisation in situ heir specificity, by analysis of TCR and response to specific antigens. The project uses basic science approaches combined with careful clinical sampling to address an important health issue. Tc2 cells likely have a role in other inflammatory diseases, infections and also cancers (such as pancreatic cancer), so defining their activity has broad implications and depending on progress, other disease areas will be explored."

关键词：免疫学与感染性疾病引起严重哮喘的免疫反应被定义为具有“2型”细胞因子偏倚。这些细胞因子包括白细胞介素4、5和13，由淋巴亚群分泌，并吸引与疾病相关的经典嗜酸性浸润。我们最近发现，在人类疾病中，肺中这些细胞因子的有效来源是CD8+ T细胞区室。分泌2型细胞因子的CD8+ T细胞表达分子CRTH2，其是PGD2（前列腺素D2）的功能性受体，并且在疾病中最富集，包括在肺中。这是一个令人惊讶的新结果（手稿正在准备中），并表明它们可能在疾病发病机制中发挥关键作用。本项目将利用从严重哮喘患者和对照组中获得的样本，通过分析TCR和对特异性抗原的反应，研究Tc2细胞对不同刺激的反应的完整功能能力Tc2细胞与上皮细胞和嗜酸性粒细胞的功能相互作用及其原位定位。该项目采用基础科学方法，结合仔细的临床抽样，以解决一个重要的健康问题。Tc2细胞可能在其他炎症性疾病、感染和癌症（如胰腺癌）中发挥作用，因此定义它们的活性具有广泛的意义，并将根据进展探索其他疾病领域。"

项目成果

Neuromedin U promotes human type 2 immune responses.

• DOI: 10.1038/s41385-022-00543-6
• 发表时间: 2022-05
• 期刊: MUCOSAL IMMUNOLOGY
• 影响因子: 8
• 作者: Ye, Yuan;Luo, Jian;Zeng, Ni;Jiang, Shan;Chen, Wentao;Hoyle, Ryan D.;Klenerman, Paul;Pavord, Ian D.;Xue, Luzheng
• 通讯作者: Xue, Luzheng