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狼疮易感小鼠中浆细胞样树突状细胞的表型和功能改变。

Phenotypic and functional alterations of pDCs in lupus-prone mice.

作者信息

Zhou Zhenyuan, Ma Jianyang, Xiao Chunyuan, Han Xiao, Qiu Rong, Wang Yan, Zhou Yingying, Wu Li, Huang Xinfang, Shen Nan

机构信息

Shanghai Institute of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS) &Shanghai Jiao Tong University School of Medicine (SJTUSM), Chinese Academy of Sciences (CAS), Shanghai, China.

出版信息

Sci Rep. 2016 Feb 16;6:20373. doi: 10.1038/srep20373.

DOI:10.1038/srep20373
PMID:26879679
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4754657/
Abstract

Plasmacytoid dendritic cells (pDCs) were considered to be the major IFNα source in systemic lupus erythematosus (SLE) but their phenotype and function in different disease status have not been well studied. To study the function and phenotype of pDCs in lupus-prone mice we used 7 strains of lupus-prone mice including NZB/W F1, NZB, NZW, NZM2410, B6.NZM(Sle1/2/3), MRL/lpr and BXSB/Mp mice and C57BL/6 as control mice. Increased spleen pDC numbers were found in most lupus mice compared to C57BL/6 mice. The IFNα-producing ability of BM pDCs was similar between lupus and C57BL/6 mice, whereas pDCs from the spleens of NZB/W F1 and NZB mice produced more IFNα than pDCs from the spleens of C57BL/6 mice. Furthermore, spleen pDCs from MRL-lpr and NZM2410 mice showed increased responses to Tlr7 and Tlr9, respectively. As the disease progressed, IFN signature were evaluated in both BM and spleen pDC from lupus prone mice and the number of BM pDCs and their ability to produce IFNα gradually decreased in lupus-prone mice. In conclusion, pDC are activated alone with disease development and its phenotype and function differ among lupus-prone strains, and these differences may contribute to the development of lupus in these mice.

摘要

浆细胞样树突状细胞(pDC)被认为是系统性红斑狼疮(SLE)中主要的IFNα来源,但它们在不同疾病状态下的表型和功能尚未得到充分研究。为了研究易患狼疮小鼠中pDC的功能和表型,我们使用了7种易患狼疮的小鼠品系,包括NZB/W F1、NZB、NZW、NZM2410、B6.NZM(Sle1/2/3)、MRL/lpr和BXSB/Mp小鼠,并以C57BL/6小鼠作为对照。与C57BL/6小鼠相比,大多数狼疮小鼠的脾脏pDC数量增加。狼疮小鼠和C57BL/6小鼠骨髓pDC产生IFNα的能力相似,而NZB/W F1和NZB小鼠脾脏中的pDC比C57BL/6小鼠脾脏中的pDC产生更多的IFNα。此外,MRL-lpr和NZM2410小鼠的脾脏pDC分别对Tlr7和Tlr9的反应增强。随着疾病进展,对易患狼疮小鼠的骨髓和脾脏pDC中的IFN特征进行了评估,在易患狼疮的小鼠中,骨髓pDC的数量及其产生IFNα的能力逐渐下降。总之,pDC随着疾病发展而被单独激活,其表型和功能在易患狼疮的品系中有所不同,这些差异可能导致这些小鼠发生狼疮。

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