Identification of organ-specific cell surface molecules on T cells and endothelial cells in patients with systemic lupus erythematosus

系统性红斑狼疮患者 T 细胞和内皮细胞上器官特异性细胞表面分子的鉴定

基本信息

批准号：
13470109
负责人：
TANAKA Yoshiya
金额：
$ 8.7万
依托单位：
University of Occupational and Environmental Health, Japan
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

Systemic lupus erythematosus (SLE) is a representative autoimmune disease, which is involved in multiple organs such as skin, kidney, central nervous system, lung and so on, and sometimes results in severe prognosis. However, the precise pathological mechanisms of each organ involvement and specific treatments for them remain unclear. We have intensively studied the mechanism of circulating T cell migration into tissues through binding with endothelial cells. Recent progress in the field clarifies certain homing molecules on T cells and endothelial cells could define organ-specific homing of T cells. In this study, we first estimated the molecules on peripheral T cells in SLE patients with skin involvement. T cells, especially Th2 cells and Tc2 cells, of SLE with skin involvement characteristically highly expressed cutaneous lymphocyte-associated antigen (CLA), whereas T cells of SLE without skin lesion possessed marginal amounts of CLA, indicating that CLA might play a role in skin ra … More sh of SLE. Next, we assessed expression of specific gene on endothelial cells purified from skin, bone/bone marrow, lung, kidney, joint, thyroid and brain, using gene chip analyses. Each endothelial cells express very interesting genes and among them, for instance, endothelial cells from synovial membrane highly expressed CD40L, enkephalin, tetranectin, C1-inhibitor, CSF-1, IL-1R, SDF-1 and so on. Based on these chip analyses would warrant further studies in the context of organ-tropism. Finally, we assessed cell surface co-stimulatory molecules on SLE T cells. Interestingly, CD28 was reduced or decreased on active SLE T cells, whereas CD29 was highly up-regulated on them. When CD29 was crosslinked by specific antibodies, T cells were efficiently activated through FAK-tyrosine kinase and CD40L and CD69 were rapidly induced on the cells. Combined with other results, CD29 could play a potent role in SLE T cell activation, in an independent manner on CD28, resulting in organ involvement such as lupus nephritis. Taken together, to clarify the mechanisms of organ-tropic involvement in SLE, as shown in the study, could lead to more specific therapeutic approaches to SLE. Less

系统性红斑狼疮（SLE）是一种代表性的自身免疫性疾病，累及皮肤、肾脏、中枢神经系统、肺等多个器官，有时导致严重的预后，但各器官受累的确切病理机制尚不清楚。我们深入研究了循环 T 细胞通过与内皮细胞结合迁移到组织的机制，阐明了 T 细胞和内皮细胞上的某些归巢分子。在这项研究中，我们首先评估了皮肤受累的 SLE 患者外周 T 细胞上的分子，特别是 Th2 细胞和 Tc2 细胞，其中皮肤受累的特征是高表达的皮肤淋巴细胞相关性。抗原（CLA），而没有皮肤病变的 SLE T 细胞含有少量的 CLA，这表明 CLA 可能在 SLE 的皮肤损伤中发挥作用。接下来，我们评估了从纯化的内皮细胞上特定基因的表达。使用基因芯片分析皮肤、骨髓、肺、肾、关节、甲状腺和大脑，每个内皮细胞都表达非常有趣的基因，其中，例如来自滑膜的内皮细胞高表达CD40L、脑啡肽、四连蛋白、C1。 -抑制剂、CSF-1、IL-1R、SDF-1 等基于这些芯片分析将需要在器官向性的背景下进行进一步研究。 SLE T 细胞上的共刺激分子高度暗示，活跃的 SLE T 细胞上的 CD28 减少或减少，而 CD29 上调，当 CD29 被特异性抗体交联时，T 细胞通过 FAK-酪氨酸激酶被有效激活。 CD40L 和 CD69 在细胞上快速诱导，结合其他结果，CD29 可以以独立于 CD28 的方式在 SLE T 细胞激活中发挥有效作用，从而导致器官受累，例如：综上所述，如研究所示，阐明系统性红斑狼疮的器官相关机制可能会导致针对系统性红斑狼疮的更具体的治疗方法。