Role of EPCR in gamma delta T cell wound healing functions

描述（由申请人提供）：蛋白C通路在凝血、炎症和伤口愈合中起重要作用。内皮蛋白C受体（EPCR）是活化蛋白C （APC）的特异性受体。EPCR由人角质形成细胞表达，可促进正常皮肤稳态和伤口愈合中的细胞存活、生长和迁移。有趣的是，EPCR最近被描述为内皮细胞和上皮肿瘤上的应激调节分子，可以直接结合人类V？4V - 5 T细胞受体并诱导T细胞扩增以应对巨细胞病毒感染和恶性肿瘤。EPCR是一种1型跨膜蛋白，其结构与MHC分子相似，并结合类似CD1d的脂质。总之，这些发现提出了EPCR可能刺激应激反应的可能性？T细胞在不同条件下，包括组织损伤。事实上,?驻留在上皮组织中的T细胞是抵御感染和创伤的关键第一道防线

DESCRIPTION (provided by applicant): The protein C pathway plays important roles in coagulation, inflammation and wound healing. The endothelial protein C receptor (EPCR) is the specific receptor for activated protein C (APC). EPCR is expressed by human keratinocytes and may promote cell survival, growth and migration in normal skin homeostasis and wound healing. Interestingly, EPCR was recently described as a stress- regulated molecule on endothelial cells and epithelial tumors that could directly bind to a human V?4V¿5 T cell receptor and elicit expansion of the T cells in response to CMV infection and malignancy. EPCR is a type 1 transmembrane protein that is structurally similar to MHC molecules and binds lipids analogous to CD1d. Together these findings raise the possibility that EPCR may stimulate the stress response of ?¿ T cells under different conditions, including tissue damage. Indeed, ?¿ T cells that reside in epithelial tissues provide a crucial first line of defense against infection, trauma and malignancy. In the skin, dendritic epidermal T cells (DETC) express a monoclonal V?3V¿1 TCR that recognizes an unknown antigen expressed by damaged or diseased keratinocytes. We propose to test the hypothesis that EPCR can provide a stress-signal of damage or disease in the epidermis to neighboring DETC to activate their wound healing functions. We will test this hypothesis by determining if the DETC TCR can interact with EPCR and by investigating whether EPCR expression during wound healing impacts epidermal ?¿ T cell wound healing responses. If found to be a prototypic stress-signal for ?¿ T cell activation, EPCR may then be a useful target in future strategies to improve healing of chronic wounds as well as other skin inflammatory diseases and malignancies.