ROLE OF TH2 CELLS IN EOTAXIN REGULATION

哮喘是一种以嗜酸性粒细胞增多症为主要组织学特征的呼吸道炎症疾病。嗜酸性粒细胞可以释放毒性介质、脂质和促炎细胞因子，从而诱导呼吸道高反应性。因此，确定将嗜酸性粒细胞招募到损伤部位所涉及的机制对于了解疾病的发病机制至关重要。趋化因子是一类分泌的蛋白质家族，在引导不同类型的白细胞到达组织损伤的感染部位起着关键作用。这项建议的目的是研究Th2细胞在调节嗜酸性粒细胞特异性趋化因子-嗜酸性粒细胞趋化因子表达中的作用。我们希望鉴定和鉴定Th2细胞释放的分子或因子，这些分子或因子在mRNA和蛋白质水平上影响Eoaxin的表达。然后，我们希望找出在促进嗜酸性粒细胞趋化蛋白基因表达方面起重要作用的转录因子。这些分子的重要性将在活体内使用现有的基因敲除动物进行检验。这项工作将有助于更好地理解Th2细胞和嗜酸性粒细胞哮喘的作用。

Asthma is a disease of airway inflammation in which airway eosinophilia is a prominent histologic feature. Eosinophils can release toxic mediators, lipids and pro-inflammatory cytokines that can induce airway hyper- responsiveness. Identifying the mechanisms that are involved in recruiting eosinophils to the site of injury are therefore critical in the understanding of pathogenesis of disease. Chemokines are a family of secreted proteins that play a critical role in directing different types of leukocytes to the site of infection of tissue damage. The aim of this proposal is to examine the role of Th2 cells in regulating the expression of eotaxin, a chemokine specific for eosinophils. We hope to identify and characterize molecules or factors released from Th2 cells that are responsible for affecting the expression of eotaxin at the mRNA and protein levels. We then hope to identify transcription factors that are important in promoting gene expression of eotaxin. The importance of these molecules will be examined in vivo using existing knockout animals. This work will lead to the greater understanding of the role of Th2 cells and eotaxin asthma.