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， 在儿童和成人中毁容的皮疹。免疫组织 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， 抗原呈递细胞，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 淋巴细胞在银屑病的发病机制中是最重要的 并包括研究表明：有效的T细胞免疫抑制 诸如环孢菌素和FK 506（他克莫司）的药物引起退化 停药后复发的牛皮癣。 T细胞共刺激分子对之间的相互作用， 假设银屑病皮肤中的专职和组织APC配体 在慢性病的发生和延续中起着重要作用 银屑病期间观察到的炎症变化。T细胞的相互作用 皮肤免疫细胞表面分子及其配体 包括但不限于LFA-1（CD 11 a/CD 18）/ICAM-1和CD 28/BB 1。 体外粘附试验证明了粘附相互作用 在T细胞表面分子CD 6和CD 6细胞表面配体之间 在γ-干扰素激活的角质形成细胞中表达。CD 6有 以前已经证明在T细胞应答过程中是重要的， 标称、同种和自身抗原。我们现在假设 皮肤免疫细胞中T细胞CD 6和CD 6配体的表达可能代表了一种新的 这是重要的启动和/或延续的途径， 牛皮癣的炎症反应。 为了确定 CD 6/CD 6配体相互作用在银屑病皮肤中的作用，本申请 提出资助表征CD 6和CD 6配体的表达， 在银屑病皮肤中表达，并通过生物化学方法鉴定这些皮肤 免疫细胞CD 6配体。