Role of EPCR in gamma delta T cell wound healing functions

EPCR 在 γδT 细胞伤口愈合功能中的作用

• 批准号: 8571495
• 负责人: Wendy L. Havran
• 金额: $ 26.72万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-05 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8571495
• 关键词: Acute; Antigens; Binding; Biological Assay; Cell Survival; Chronic; Coagulation Process; Cytomegalovirus; Disease; Endothelial Cells; Epidermis; Epithelial; Future; Growth; Healed; Homeostasis; Human; Immigration; Infection; Inflammation; Inflammatory; Integral Membrane Protein; Knockout Mice; Lipid Binding; Malignant - descriptor; Malignant Neoplasms; Mus; Pathway interactions; Patients; Play; Protein C; Regulation; Role; Signal Transduction; Skin; Skin Tissue; Specificity; Stress; T-Cell Activation; T-Cell Receptor; T-Lymphocyte; Testing; Tissues; Trauma; Wound Healing; activated protein C receptor; biological adaptation to stress; healing; improved; keratinocyte; mouse model; public health relevance; receptor; receptor binding; receptor expression; response; therapeutic target; tissue repair; tumor; wound

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.

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。内皮细胞蛋白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，并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，可以直接与人V？4V_5 T细胞受体，并引发T细胞响应CMV感染和恶性肿瘤的扩增。EPCR是一种1型跨膜蛋白，其结构类似于MHC分子，并结合类似于CD1d的脂质。 总之，这些发现提高了EPCR可能刺激应激反应的可能性。T细胞在不同的条件下，包括组织损伤。是吗？上皮组织中的T细胞提供了对抗感染、创伤 和恶性肿瘤在皮肤中，树突状表皮T细胞（DETC）表达单克隆V？识别由受损或患病的角质形成细胞表达的未知抗原的3V1 TCR。我们建议测试的假设，EPCR可以提供一个应力信号的损伤或疾病的表皮相邻的DETC激活其伤口愈合功能。 我们将通过确定DETC TCR是否可以与EPCR相互作用以及通过调查伤口愈合过程中EPCR表达是否影响表皮来验证这一假设。T细胞伤口愈合反应。 如果被发现是一个原型的压力信号？T细胞活化，EPCR可能是未来改善慢性伤口愈合以及其他皮肤炎性疾病和恶性肿瘤的有用目标。