Role of CXCR3 in Th1-Mediated Lung Injury

CXCR3 在 Th1 介导的肺损伤中的作用

• 批准号: 6950504
• 负责人: Anne M. Manicone
• 金额: $ 4.23万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6950504
• 关键词: Role; CXCR3; Th1; Mediated; Lung

DESCRIPTION (provided by applicant): CXCR3 and its ligands are associated with Th1-related responses including allograft rejection and bronchiolitis obliterans. Reduced allograft rejection in CXCR3 knockout mice (KO) suggests an important and non-redundant role of this chemokine receptor. Activated Th1-cells are the predominant expressers of CXCR3, and more recent studies indicate that there is a small population of CXCR3 (+) myeloid cells. Although the role of these CXCR3 (+) myeloid cells is unknown, chemokine receptors may define and recruit populations of myeloid cells with specific effector or accessory functions. In our murine model of Th1-induced lung, CXCR3 ligands appear to be important inflammatory mediators, and host lymphocytes (the predominant expressers of CXCR3) are not required. This preliminary work suggests a role for CXCR3 (+) myeloid cells in lung injury, and we hypothesize that (1) CXCR3 (+) myeloid cells are required for the inflammatory response to Thl cells and (2) these cells secrete proinflammatory cytokines that are critical to the inflammatory response. The goal of this project is to determine the role of CXCR3 (+) myeloid cells in Thl-mediated lung injury, which will lead to a better understanding of other Th1-associated diseases.

描述(申请人提供)：CXCR3及其配体与Th1相关反应有关，包括同种异体移植排斥反应和闭塞性毛细支气管炎。在CXCR3基因敲除小鼠(KO)中减少同种异体移植排斥反应表明这种趋化因子受体的一个重要的和非多余的作用。活化的Th1细胞是CXCR3的主要表达细胞，最近的研究表明存在少量的CXCR3(+)髓系细胞。虽然这些CXCR3(+)髓系细胞的作用尚不清楚，但趋化因子受体可能定义和招募具有特定效应或辅助功能的髓系细胞群。在我们的Th1诱导的小鼠肺模型中，CXCR3配体似乎是重要的炎症介质，而宿主淋巴细胞(CXCR3的主要表达者)不是必需的。这项初步工作提示CXCR3(+)髓系细胞在肺损伤中的作用，我们假设(1)CXCR3(+)髓系细胞是THL细胞炎症反应所必需的，(2)这些细胞分泌对炎症反应至关重要的促炎细胞因子。本项目的目标是确定CXCR3(+)髓系细胞在Th1介导的肺损伤中的作用，这将有助于更好地了解其他Th1相关疾病。