The role of osteopontin in the induction of the CD40 ligand in Graves' disease
The role of osteopontin in the induction of the CD40 ligand in Graves' disease
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DOI：
10.1111/cen.12229
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发表时间：
2014-01-01
影响因子：
3.2
通讯作者：
Wang, Shu
中科院分区：
文献类型：
--
作者：
Qi, Yicheng;Li, Xiaoli;Wang, Shu
目的Graves病(GD)是一种常见的自身免疫性疾病，涉及自身抗体的产生。尽管我们以前报道过骨桥蛋白(OPN)是一种促炎蛋白，通过激活核因子-B来影响GD的发展，但关于OPN在GD免疫球蛋白产生中的调节作用还知之甚少。CD40配体(CD40L)表达于活化的CD4+T细胞表面，共刺激B细胞表面的CD40，刺激免疫球蛋白的产生，这一过程已被报道在多种自身免疫性疾病的免疫信号转导中发挥重要作用。本研究旨在探讨CD40L与GD发生发展的关系，并探讨OPN通过CD40L调节GD免疫球蛋白生成的作用。检测CD40L膜结合型和可溶性CD40L，并分析其与临床参数的相关性。此外，还分析了OPN与CD40L水平的相关性。结果GD患者CD40L水平明显升高，缓解期患者CD40L水平有所恢复。CD40L水平与GD临床诊断参数及OPN浓度相关。此外，人重组OPN和GD患者血浆中CD40L的表达增加，OPN单抗可显著抑制CD40L的表达。此外，CD40L抗体可阻断OPN对GD患者和正常人外周血单个核细胞(PBMC)免疫球蛋白产生的促进作用。结论CD40L是由OPN诱导产生的，是OPN在GD发病过程中产生免疫球蛋白的下游效应分子。
ObjectiveGraves' disease (GD) is a common autoimmune disease involved autoantibody production. Although we previously reported that osteopontin (OPN), a proinflammatory protein, affected development of GD through NF-B activation, little is known about the role of OPN in regulating immunoglobulin production in GD. CD40 Ligand (CD40L) is expressed on the surface of activated CD4+T cells and costimulates CD40 on B cells, stimulating production of immunoglobulins, a process which has been reported to play a vital role in immunological signalling transduction in several autoimmune diseases. This study sought to characterize the relationship between CD40L and GD development, as well as investigating the role of OPN in modulating immunoglobulin production in GD via CD40L.MethodsForty incident patients with GD, twenty-one patients with GD in remission and twenty-seven healthy controls were recruited. Both membrane-bound and soluble forms of CD40L were measured, and their correlations with clinical parameters were studied. In addition, correlation between OPN and CD40L level was also examined. Furthermore, we studied the regulatory effect of OPN on CD40L in CD4+T cells.ResultsWe demonstrated that the CD40L levels were enhanced in patients with GD and recovered in patients with GD in remission. CD40L levels correlated with clinical GD diagnostic parameters and OPN concentration. Moreover, human recombinant OPN and plasma samples from patients with GD increased CD40L expression, which could be significantly suppressed by OPN monoclonal antibody. In addition, CD40L antibody blocked the immunoglobulin production augmented by OPN in cultured peripheral blood mononuclear cells (PBMCs), isolated from patients with GD and healthy subjects.ConclusionThese results indicate that CD40L is induced by OPN and serves as the downstream effector of OPN for immunoglobulin production in GD development.