Gpr97/Adgrg3 ameliorates experimental autoimmune encephalomyelitis by regulating cytokine expression
Gpr97/Adgrg3 ameliorates experimental autoimmune encephalomyelitis by regulating cytokine expression
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Gpr97/Adgrg3 通过调节细胞因子表达改善实验性自身免疫性脑脊髓炎
DOI：
10.1093/abbs/gmy060
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发表时间：
2018-07-01
影响因子：
3.7
通讯作者：
Wang, Zhugang
中科院分区：
文献类型：
--
作者：
Wang, Jinjin;Wang, Xiyi;Wang, Zhugang
多发性硬化症及其主要动物模型实验性自身免疫性脑脊髓炎（EAE）是一种以免疫介导的脱髓鞘和神经退行性变为特征的中枢神经系统（CNS）炎症性疾病，可能通过抑制核因子-κB （NF-κB）信号通路介导。据报道，由Adgrg3编码的Gpr97可调节NF-κB的活性。在这项研究中，我们利用先前建立的adgrg3敲除小鼠模型，研究了Gpr97在小鼠自身免疫性中枢神经系统疾病发展中的作用。我们发现EAE小鼠脊髓中Adgrg3的表达明显增加。与对照组相比，患有EAE的Adgrg3缺陷（Adgrg3-/-）小鼠表现出峰值严重程度和累积疾病评分增加，随后白细胞浸润显著增加，脱髓鞘更广泛。Adgrg3-/-小鼠中枢神经系统中Th1/Th17细胞的百分比显著增加，并伴有高水平的白细胞介素(IL)-6、干扰素-γ、肿瘤坏死因子-α和IL-17。体外培养实验证实Gpr97调节促炎细胞因子的产生。综上所述，我们的研究结果表明Gpr97在EAE的发展中起着重要作用，并且可能具有治疗中枢神经系统自身免疫的潜力。
Multiple sclerosis and its primary animal model, experimental autoimmune encephalomyelitis (EAE), are inflammatory diseases of the central nervous system (CNS) characterized by immune-mediated demyelination and neurodegeneration that may be mediated by inhibition of the nuclear factor-κB (NF-κB) signaling pathway. Gpr97, encoded by Adgrg3, has been reported to regulate the activity of NF-κB. In this study, using a previously established Adgrg3-knockout mouse model, we investigated the roles of Gpr97 in the development of autoimmune CNS disease in mice. We found a marked increase in the expression of Adgrg3 in spinal cords of mice with EAE. Adgrg3-deficient (Adgrg3-/-) mice with EAE exhibited increases in peak severity and the cumulative disease score compared with littermate controls, followed by a notable increase of leukocyte infiltration and more extensive demyelination. The percentages of Th1/Th17 cells in the CNS were significantly increased in Adgrg3-/- mice and accompanied by high levels of interleukin (IL)-6, interferon-γ, tumor necrosis factor-α, and IL-17. An in vitro culture assay verified that Gpr97 regulated proinflammatory cytokine production. Taken together, our results show that Gpr97 plays an important role in the development of EAE and may have a therapeutic potential for the treatment of CNS autoimmunity.