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MOSPD2 is a therapeutic target for the treatment of CNS inflammation.
Clinical & Experimental Immunology ( IF 4.6 ) Pub Date : 2020-04-30 , DOI: 10.1111/cei.13448
N Yacov 1 , P Kafri 1 , Y Salem 1 , O Propheta-Meiran 1 , B Feldman 1 , E Breitbart 1 , I Mendel 1
Affiliation  

In multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), myeloid cells comprise a major part of the inflammatory infiltrate in the central nervous system (CNS). We previously described that motile sperm domain‐containing protein 2 (MOSPD2) is expressed on human myeloid cells and regulates monocyte migration in vitro . The role of MOSPD2 in EAE pathogenesis was studied by generating MOSPD2 knock‐out (KO) mice and monoclonal antibodies directed against MOSPD2. We found that EAE development in MOSPD2 KO mice was significantly suppressed. While frequency representation of leukocyte subsets in lymphoid tissues was comparable, the ratio of inflammatory monocytes in the blood was markedly reduced in MOSPD2 KO mice. In addition, T cells from MOSPD2 KO mice displayed reduced secretion of proinflammatory cytokines and increased production of interleukin (IL)‐4. Prophylactic and post‐onset treatment using monoclonal antibodies (mAbs) generated against MOSPD2 abrogated development and reduced EAE severity. These results suggest that MOSPD2 is key in regulating migration of inflammatory monocytes, and that anti‐MOSPD2 mAbs constitute a potential therapy for the treatment of CNS inflammatory diseases.

中文翻译:

MOSPD2是治疗中枢神经系统炎症的治疗靶标。

在多发性硬化症和实验性自身免疫性脑脊髓炎(EAE)中,髓样细胞构成了中枢神经系统(CNS)炎性浸润的主要部分。我们之前曾描述过,运动精子域蛋白2(MOSPD2)在人骨髓细胞上表达并在体外调节单核细胞迁移。通过产生MOSPD2敲除(KO)小鼠和针对MOSPD2的单克隆抗体,研究了MOSPD2在EAE发病机理中的作用。我们发现MOSPD2 KO小鼠中的EAE发育被显着抑制。虽然淋巴组织中白细胞亚群的频率表示具有可比性,但在MOSPD2 KO小鼠中,血液中炎性单核细胞的比例显着降低。此外,来自MOSPD2 KO小鼠的T细胞显示出促炎细胞因子的分泌减少,白介素(IL)-4的产生增加。使用针对MOSPD2产生的单克隆抗体(mAb)进行预防和发作后治疗,可消除发育并降低EAE严重程度。这些结果表明,MOSPD2是调节炎症性单核细胞迁移的关键,
更新日期:2020-04-30
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