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类风湿关节炎外周血CD4淋巴细胞趋化因子受体的表达:CCR7与CD95的共表达与疾病活动相关。

Chemokine receptors expression on peripheral CD4-lymphocytes in rheumatoid arthritis: Coexpression of CCR7 and CD95 is associated with disease activity.

作者信息

Aldahlawi Alia M, Elshal Mohammed F, Ashgan Fai T, Bahlas Sami

机构信息

Biological Sciences Department, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia ; Immunology Unit, King Fahad Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.

Biochemistry Department, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia ; Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute, Sadat City University, Sadat City, Egypt.

出版信息

Saudi J Biol Sci. 2015 Jul;22(4):453-8. doi: 10.1016/j.sjbs.2015.02.011. Epub 2015 Feb 14.

DOI:10.1016/j.sjbs.2015.02.011
PMID:26150752
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4487268/
Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation triggered by infiltrating CD4 lymphocytes. The positioning and activation of lymphocyte in inflamed synovial tissues are dependent on a number of factors including their chemokine receptor expression profile. We aimed to investigate which chemokine receptors pattern correlate with serum cytokine levels and with disease activity. Forty patients with RA (34 female and 6 male) with age range from 21 to 68 years were included. Twenty healthy volunteers (16 female and 4 male) with matched age (range 21-48 years) were served as healthy controls (HCs). Expression of chemokine receptors (CCR5, CX3CR1 and CCR7) together with the apoptosis-related marker (CD95) was analyzed using three-color flow cytometry analysis after gating on CD4(+) peripheral blood lymphocytes. Plasma levels of IL-6, IL-10, IL-12 and TNF-α cytokines were measured in all participants using ELISA. Disease activity score (DAS28-CRP) system was assessed and active disease was defined as DAS28 ⩾3.2. Twenty-five (62.4%) patients were classified as active RA (ARA) and 15 (37.5%) patients with inactive RA (IRA). Percentages of CD4(+) lymphocytes expressing CD95 with either of CCR7 or CCR5 were significantly higher in ARA compared to IRA and HCs groups, while the expression of CX3CR1 on T-cells was found significantly lower in both CD95(-) and CD95(+) T-cells in RA groups than HC. Percentages of CD4(+)CD95(+)CCR7(+) cells correlated positively with IL-6 (r = 0.390). Whereas CD4(+)CD95(+)CX3CR1(+) were negatively correlated with TNF-α (r = -0.261). Correlation of CD4(+)CD95(+)CCR7(+) T cell subset with disease activity and inflammatory cytokines suggests a role for this cell subset in the pathogenesis of RA. Further investigation will be required to fully characterize this cell subset and its role in disease progression.

摘要

类风湿性关节炎(RA)是一种慢性自身免疫性疾病,其特征是由浸润的CD4淋巴细胞引发滑膜炎症。淋巴细胞在炎症滑膜组织中的定位和激活取决于多种因素,包括它们的趋化因子受体表达谱。我们旨在研究哪些趋化因子受体模式与血清细胞因子水平及疾病活动相关。纳入了40例年龄在21至68岁之间的RA患者(34例女性和6例男性)。20名年龄匹配(范围为21至48岁)的健康志愿者(16例女性和4例男性)作为健康对照(HC)。在对CD4(+)外周血淋巴细胞进行门控后,使用三色流式细胞术分析趋化因子受体(CCR5、CX3CR1和CCR7)以及凋亡相关标志物(CD9)的表达。使用酶联免疫吸附测定法(ELISA)测量所有参与者血浆中IL-6、IL-10、IL-12和TNF-α细胞因子的水平。评估疾病活动评分(DAS28-CRP)系统,将活动性疾病定义为DAS28⩾3.2。25例(62.4%)患者被分类为活动性RA(ARA),15例(37.5%)患者为非活动性RA(IRA)。与IRA组和HC组相比,表达CCR7或CCR5之一的CD4(+)淋巴细胞中表达CD95的百分比在ARA组中显著更高,而在RA组的CD95(-)和CD95(+)T细胞中,T细胞上CX3CR1的表达均显著低于HC组。CD4(+)CD95(+)CCR7(+)细胞的百分比与IL-6呈正相关(r = 0.390)。而CD4(+)CD95(+)CX3CR1(+)与TNF-α呈负相关(r = -0.261)。CD4(+)CD95(+)CCR7(+)T细胞亚群与疾病活动和炎性细胞因子之间的相关性表明该细胞亚群在RA发病机制中起作用。需要进一步研究以全面表征该细胞亚群及其在疾病进展中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce0/4487268/5b7dded300e0/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce0/4487268/5b7dded300e0/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ce0/4487268/5b7dded300e0/gr1.jpg

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