EXPRESSION AND IDENTIFICATION OF CD6 LIGANDS IN PSORIASIS

银屑病中 CD6 配体的表达和鉴定

• 批准号: 6100499
• 负责人: NORA SINGER
• 金额: $ 4.59万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-03-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6100499
• 关键词: CD antigens; CD28 molecule; T lymphocyte; biopsy; cell adhesion; cell adhesion molecules; clinical research; human subject; inflammation; keratinocyte; leukocyte adhesion molecules; psoriasis; tissue /cell culture

Psoriasis is a chronic inflammatory skin disease which causes disfiguring skin eruptions in children and adults. Immunohistologic studies of psoriatic plaques show hyperplastic proliferation of epidermal keratinocytes juxtaposed to activated T lymphocytes and antigen presenting cells including epidermal Langerhans cells and dermal dendritic cells. Multiple lines of evidence suggest that T lymphocytes are of primary importance in the pathogenesis of psoriasis and include studies showing that: potent T-cell immunosuppressive medications such as cyclosporin and FK506 (tacrolimus) cause regression of psoriasis which returns when the medication is discontinued. Interactions between pairs of T-cell co-stimulatory molecules and professional and tissue APC ligands in psoriatic skin are hypothesized to be important in the initiation and perpetuation of the chronic inflammatory changes observed during psoriasis. Interactions of T-cell surface molecules and their ligands expressed on skin immunocytes include but are not limited to LFA-1 (CD11a/CD18)/ICAM-1, and CD28/BB1. In vitro adhesion assays have demonstrated adhesive interactions between the T-cell surface molecule CD6, and CD6 cell surface ligands expressed in gamma-interferon activated keratinocytes. CD6 has previously been shown to be important during T cell responses to nominal, allo and self antigen. We now hypothesize that interactions of T cell CD6 and CD6 ligands in skin immunocytes may represent a novel pathway which is important in initiation and/or perpetuation of the inflammatory response seen in psoriasis. In order to determine the role of CD6/CD6 ligand interactions in psoriatic skin, this application proposes funding to characterize the expression of CD6 and CD6 ligands expressed in psoriatic skin, and to biochemically identify these skin immunocyte CD6 ligands.

牛皮癣是一种慢性炎症性皮肤病，导致 儿童和成人的皮肤爆发毁容。免疫组织学 银屑病斑块的研究显示 表皮角质形成细胞与活化的T淋巴细胞并列 抗原呈现细胞，包括表皮朗格汉斯细胞和 真皮树突状细胞。多种证据表明T 淋巴细胞在牛皮癣的发病机理中至关重要 并包括：有效的T细胞免疫抑制作用的研究 Cyclosporin和FK506（他克莫司）等药物会导致回归 牛皮癣，当药物停产时返回。 T细胞共刺激分子对之间的相互作用与 假设银屑病皮肤中的专业和组织APC配体被假设 对于慢性的启动和延续很重要 牛皮癣期间观察到的炎症变化。 T细胞的相互作用 表面分子及其在皮肤免疫细胞上表达的配体 包括但不限于LFA-1（CD11A/CD18）/ICAM-1和CD28/BB1。 体外粘附测定已显示出粘合性相互作用 在T细胞表面分子CD6和CD6细胞表面配体之间 在伽马 - 互换中表达活化的角质形成细胞。 CD6具有 以前在T细胞对 名义上的Allo和自我抗原。我们现在假设互动 皮肤免疫细胞中的T细胞CD6和CD6配体可能代表一种新颖的 在开始和/或延续的途径 牛皮癣中看到的炎症反应。 为了确定 CD6/CD6配体相互作用在银屑病皮肤中的作用，该应用 提出资金来表征CD6和CD6配体的表达 在银屑病皮肤中表达，并在生化上识别这些皮肤 免疫细胞CD6配体。