CD1-lipid reactivity of epidermal T cells

表皮 T 细胞的 CD1-脂质反应性

• 批准号: 9050634
• 负责人: Wendy L. Havran
• 金额: $ 20.85万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-08 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9050634
• 关键词: Antigens; Autoimmune Diseases; Binding; Blood; Cells; Ceramides; Characteristics; Cloning; Complex; Data; Dermal; Disease; Epidermis; Future; Generations; Healed; Human; Individual; Inflammation; Inflammatory; Intestines; Langerhans cell; Lipid Binding; Lipids; Microbe; Mus; Oils; Population; Proteins; Reporting; Sebaceous Glands; Sebum; Series; Signal Transduction; Skin; Skin Neoplasms; Source; Squalene; Stress; Sulfoglycosphingolipids; T-Lymphocyte; Testing; Wound Healing; chronic wound; healing; improved; keratinocyte; peripheral blood; public health relevance; response

DESCRIPTION (provided by applicant): Since the initial discovery of γδ cells 30 years ago, non-classical MHC molecules have been proposed as antigens or antigen presenting molecules for these cells. In the intervening years, individual T cell clones have been identified with reactivity to CD1 and TL molecules but MHC reactivity has not been shown for populations of γδ cells. Recent data from two groups has now shown that the Vδ1+ TCR from human peripheral blood and intestinal γδ cells can directly bind to CD1d-αGalCer and CD1d-sulfatide. Interestingly, the Vδ1+ TCR is also used by epidermal-resident γδ cells in both human and mouse skin. CD1 expression is upregulated on epidermal cells during skin inflammation and disease and the epidermis is a rich source of lipids and skin oils. This raises the possibility tha CD1-lipid reactivity may be characteristic of all Vδ1+ T cells, including those that are resident i the epidermis. We propose to test the hypothesis that CD1-skin lipid antigens can provide a stress-signal of damage or disease in the epidermis to neighboring Vδ1+ T cells to activate their wound healing functions. We will test this hypothesis by determining if the human or mouse Vδ1+ TCR can interact with CD1-lipid antigens and by investigating whether CD1d expression during wound healing impacts epidermal γδ cell wound healing responses. If found to be a prototypic stress-signal for γδ cell activation, CD1 or skin lipids may then be considered as targets in future strategies to improve healing of chronic wounds as well as other skin inflammatory or autoimmune diseases.

描述（由申请人提供）：自30年前首次发现γδ细胞以来，已提出将非经典MHC分子作为这些细胞的抗原或抗原呈递分子。在此期间，已经鉴定出单个T细胞克隆具有对CD 1和TL分子的反应性，但尚未显示γδ细胞群体的MHC反应性。两个研究小组的最新数据表明，来自人外周血和肠道γδ细胞的Vδ1+ TCR可以直接与CD 1d-αGalCer和CD 1d-硫苷脂结合。有趣的是，人和小鼠皮肤中的表皮驻留γδ细胞也使用Vδ1+ TCR。在皮肤炎症和疾病期间，表皮细胞上的CD 1表达上调，并且表皮是脂质和皮肤油的丰富来源。这增加了CD 1-脂质反应性可能是所有Vδ1+ T细胞的特征的可能性，包括那些驻留在表皮中的T细胞。我们建议测试的假设，CD 1-皮肤脂质抗原可以提供一个应力信号的损伤或疾病的表皮相邻的Vδ1+ T细胞，以激活他们的伤口愈合功能。我们将通过确定人或小鼠Vδ1+ TCR是否可以与CD 1-脂质抗原相互作用以及研究伤口愈合期间CD 1d表达是否影响表皮γδ细胞伤口愈合反应来验证这一假设。如果发现CD 1或皮肤脂质是γδ细胞活化的原型应激信号，则可以将其视为未来策略的目标，以改善慢性伤口以及其他皮肤炎性或自身免疫性疾病的愈合。