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（SLE）是一种具有代表性的自身免疫性疾病，累及皮肤、肾脏、中枢神经系统、肺等多脏器，有时预后严重。然而，每个器官受累的确切病理机制和具体的治疗方法仍不清楚。我们深入研究了循环T细胞通过与内皮细胞结合向组织迁移的机制。近年来该领域的研究进展表明，T细胞和内皮细胞上的某些归巢分子可以定义T细胞的器官特异性归巢。在这项研究中，我们首先估计了SLE患者皮肤受累时外周T细胞上的分子。累及皮肤的SLE患者的T细胞，尤其是Th2细胞和Tc2细胞具有高表达皮肤淋巴细胞相关抗原（CLA）的特征，而无皮肤病变的SLE患者的T细胞具有少量的CLA，表明CLA可能在SLE的皮肤ra中发挥作用。接下来，我们利用基因芯片分析评估了特定基因在皮肤、骨/骨髓、肺、肾、关节、甲状腺和脑内皮细胞上的表达。每一种内皮细胞都表达非常有趣的基因，其中滑膜内皮细胞高表达CD40L、脑啡肽、四联素、c1抑制剂、CSF-1、IL-1R、SDF-1等。基于这些芯片分析将保证在器官向性的背景下进一步研究。最后，我们评估了SLE T细胞的细胞表面共刺激分子。有趣的是，CD28在活动性SLE T细胞上减少或减少，而CD29在活动性SLE T细胞上高度上调。当CD29与特异性抗体交联后，通过fak -酪氨酸激酶有效激活T细胞，并快速诱导CD40L和CD69上细胞。结合其他结果，CD29可能在SLE T细胞激活中发挥强有力的作用，以CD28独立的方式，导致器官受累，如狼疮肾炎。综上所述，如本研究所示，阐明SLE中嗜器官受累的机制，可能会导致更具体的SLE治疗方法。少

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