Critical roles of CXC chemokine ligand 16/scavenger receptor that binds phosphatidylserine and oxidized lipoprotein in the pathogenesis of both acute and adoptive transfer experimental autoimmune encephalomyelitis
Critical roles of CXC chemokine ligand 16/scavenger receptor that binds phosphatidylserine and oxidized lipoprotein in the pathogenesis of both acute and adoptive transfer experimental autoimmune encephalomyelitis
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DOI：
10.4049/jimmunol.173.3.1620
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发表时间：
2004-08-01
影响因子：
4.4
通讯作者：
Yonehara, S
中科院分区：
文献类型：
--
作者：
Fukumoto, N;Shimaoka, T;Yonehara, S
结合磷脂酰丝氨酸和氧化型脂蛋白(SR-PSOX)/CXCL16的清道夫受体是一种表达于巨噬细胞和树突状细胞的趋化因子，其受体表达于T细胞和NK T细胞。我们研究了SR-PSOX/CXCL16在急性过继实验性自身免疫性脑脊髓炎(EAE)中的作用。EAE是一种Th1极化T细胞介导的中枢神经系统自身免疫性疾病。在初次免疫前后应用抗SR-PSOX/CXCL16的单抗可降低急性EAE的发病率，同时减少单个核细胞对中枢神经系统的渗透。给药也被证明能抑制初次免疫反应时血清干扰素-γ水平的升高，以及随后产生的抗原特异性T细胞。在过继转移性EAE中，用抗SR-PSOX/CXCL16单抗治疗受体小鼠不仅可降低临床发病率，而且可减少单个核细胞进入中枢神经系统。此外，组织病理学分析表明，EAE的临床发展与SR-PSOX/CXCL16在中枢神经系统的表达密切相关。以上结果表明，SRPSOX/CXCL16通过支持抗原特异性T细胞的生成以及炎性单核细胞向中枢神经系统的募集，在EAE中发挥重要作用。
The scavenger receptor that binds phosphatidylserine and oxidized lipoprotein (SR-PSOX)/CXCL16 is a chemokine expressed on macrophages and dendritic cells, while its receptor expresses on T and NK T cells. We-investigated the role of SR-PSOX/CXCL16 on acute and adoptive experimental autoimmune encephalomyelitis (EAE), which is Th1-polarized T cell-mediated autoimmune disease of the CNS. Administration of mAb against SR-PSOX/CXCL16 around the primary immunization decreased disease incidence of acute EAE with associated reduced infiltration of mononuclear cells into the CNS. Its administration was also shown to inhibit elevation of serum IFN-gamma level at primary immune response, as well as subsequent generation of Ag-specific T cells. In adoptive transfer EAE, treatment of recipient mice with anti-SR-PSOX/CXCL16 mAb also induced not only decreased clinical disease incidence, but also diminished traffic of mononuclear cells into the CNS. In addition, histopathological analyses showed that clinical development of EAE correlates well with expression of SR-PSOX/CXCL16 in the CNS. All the results show that SRPSOX/CXCL16 plays important roles in EAE by supporting generation of Ag-specific T cells, as well as recruitment of inflammatory mononuclear cells into the CNS.