CD200-CD200R1相互作用的N-糖基化在经典小胶质细胞激活中的作用

The role of N-glycosylation of CD200-CD200R1 interaction in classical microglial activation.

作者信息

Liu Chao, Shen Yifen, Tang Ying, Gu Yongchun

机构信息

Central Lab, First People's Hospital of Wujiang Dist, Suzhou, 215200 Jiangsu Province China.

2Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 136 Hanzhong Road, Nanjing, 210029 Jiangsu Province China.

出版信息

J Inflamm (Lond). 2018 Dec 19;15:28. doi: 10.1186/s12950-018-0205-8. eCollection 2018.

BACKGROUND

Microglial inflammatory activation is the common feature of the central nervous system (CNS) diseases. Microglia can be activated and particularly polarized toward a dual role in the injured CNS. The CD200 receptor 1 (CD200R1) inhibits inflammatory microglia activation as illustrated by studies. Publications show abnormal activation of microglia secondary to the deficient inhibit of CD200-CD200R interaction. In the present study, we established a neuronal-microglia co-culture system to investigate the association between CD200R1 engagement and classical microglial activation. We analyzed the glycosylation of CD200R1 and the CD200 binding. Secretion of pro-inflammatory cytokines were measured.

RESULTS

CD200R1 was N-glycosylated at Asparagine 44 (Asn44, N44). Mutation of this site disrupted CD200-CD200R1 interaction and up-regulated the expression of cytokines iNOS, CD86, IL-1β and TNF-α.

CONCLUSION

N44 of CD200R1 is a significant binding site for CD200-CD200R1 interaction and play a critical role in the maintenance of microglia. The N-glycosylation of CD200R1 could serve as a therapeutic agent for CNS inflammation.

背景

小胶质细胞的炎症激活是中枢神经系统（CNS）疾病的共同特征。小胶质细胞可被激活，并在受损的中枢神经系统中尤其向双重作用极化。如研究所示，CD200受体1（CD200R1）抑制炎症性小胶质细胞激活。出版物表明，由于CD200 - CD200R相互作用的抑制不足，小胶质细胞出现异常激活。在本研究中，我们建立了神经元 - 小胶质细胞共培养系统，以研究CD200R1参与与经典小胶质细胞激活之间的关联。我们分析了CD200R1的糖基化和CD200结合情况。测量了促炎细胞因子的分泌。