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1,25(OH)D和维生素D受体对系统性红斑狼疮小鼠模型外周CD4/CD8双阳性T淋巴细胞的影响

Effects of 1,25(OH) D and vitamin D receptor on peripheral CD4 /CD8 double-positive T lymphocytes in a mouse model of systemic lupus erythematosus.

作者信息

Ding Yan, Liao Wang, He Xiao-Jie, Xiang Wei

机构信息

Department of Dermatology, Maternal and Child Health Care Hospital of Hainan Province, Haikou, China.

Department of Cardiology, Hainan General Hospital, Haikou, China.

出版信息

J Cell Mol Med. 2017 May;21(5):975-985. doi: 10.1111/jcmm.13037. Epub 2017 Jan 7.

Abstract

This study aims to explore effects of 1,25(OH) D and vitamin D receptor (VDR) on peripheral CD4 /CD8 double-positive (DP) T lymphocytes in systemic lupus erythematosus (SLE). MRL-LPr/LPr mice with SLE (n = 20) and normal MRL mice (n = 20) were assigned into the control group (normal mice, without feeding with 1,25(OH) D ), the 1,25(OH) D group (SLE mice, feeding with 1,25(OH) D ), the VDR-knock-in + 1,25(OH) D group (SLE mice, VDR-knock-in, feeding with 1,25(OH) D ) and the VDR-knockout group (normal mice, VDR-knockout, without feeding with 1,25(OH) D ) (n = 10 per group). Levels of T lymphocytes were measured by flow cytometry. The mRNA and proteins expressions of inflammatory factors were measured by qRT-PCR and ELISA. Extracellular signal-regulated kinase-1/2 (ERK1/2) expression was measured by Western blotting. Compared with normal mice, SLE mice showed reduced levels of CD4 , CD4 /CD8 ratio, and DP lymphocytes. The levels of SLE-related indicators all increased significantly, followed with severe skin ulcers and urinary system infection. With the increase in time, skin ulcers and urinary system infection were significantly improved, levels of CD4 , CD4 /CD8 ratio, and DP lymphocytes increased, and levels of SLE-related indicators all decreased in the 1,25(OH) D group. There were no significant changes in bioindicators in the control and the VDR-knock-in + 1,25(OH) D groups. The symptoms of SLE gradually occurred in the VDR-knockout group. This study demonstrates that VDR and 1,25(OH) D could elevate CD4 /CD8 DP T lymphocytes and reduce expressions of inflammatory factors, thus inhibiting the development and progression of SLE.

摘要

本研究旨在探讨1,25(OH)D和维生素D受体(VDR)对系统性红斑狼疮(SLE)外周血CD4/CD8双阳性(DP)T淋巴细胞的影响。将患有SLE的MRL-LPr/LPr小鼠(n = 20)和正常MRL小鼠(n = 20)分为对照组(正常小鼠,不给予1,25(OH)D)、1,25(OH)D组(SLE小鼠,给予1,25(OH)D)、VDR基因敲入+1,25(OH)D组(SLE小鼠,VDR基因敲入,给予1,25(OH)D)和VDR基因敲除组(正常小鼠,VDR基因敲除,不给予1,25(OH)D)(每组n = 10)。通过流式细胞术检测T淋巴细胞水平。采用qRT-PCR和ELISA检测炎症因子的mRNA和蛋白表达。通过蛋白质印迹法检测细胞外信号调节激酶-1/2(ERK1/2)表达。与正常小鼠相比,SLE小鼠的CD4水平、CD4/CD8比值和DP淋巴细胞水平降低。SLE相关指标水平均显著升高,随后出现严重皮肤溃疡和泌尿系统感染。随着时间的推移,1,25(OH)D组的皮肤溃疡和泌尿系统感染明显改善,CD4水平、CD4/CD8比值和DP淋巴细胞水平升高,SLE相关指标水平均降低。对照组和VDR基因敲入+1,25(OH)D组的生物指标无显著变化。VDR基因敲除组逐渐出现SLE症状。本研究表明,VDR和1,25(OH)D可升高CD4/CD8 DP T淋巴细胞水平,降低炎症因子表达,从而抑制SLE的发生发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8280/5387123/586b7379f17a/JCMM-21-975-g001.jpg

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