Role of CXCR3 in Th1-Mediated Lung Injury

点击翻译按钮获取中文摘要

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.