Rheumatology Unit, Department of Medical Sciences, University of Ferrara and Azienda Ospedaliero-Universitaria Sant'Anna, Cona, Italy.
Experimental Laboratory of Immunological and Rheumatologic Researches, Istituto Auxologico Italiano, IRCCS, Milan, Italy.
Front Immunol. 2020 Oct 29;11:572876. doi: 10.3389/fimmu.2020.572876. eCollection 2020.
Patients with systemic lupus erythematosus (SLE) have a significant increase in cardiovascular (CV) risk although they display a preserved number of circulating angiogenic CD3CD31CXCR4 T cells (T), a subpopulation of T cells which promotes repair of damaged endothelium. This happens due to the concomitant expansion of a T subset with immunosenescent features, such as the loss of CD28. Therefore, the aim of this study was to elucidate the interplay between T subpopulations and endothelial cells in a group of young SLE patients without previous cardiovascular events. Twenty SLE female patients and 10 healthy controls (HCs) were recruited. Flow cytometric analysis of endothelial progenitor cells (EPCs) and T subsets were performed and serum levels of interleukin (IL)-6, -8, matrix metalloproteinase (MMP)-9 and interferon (IFN)- were measured. Human umbilical vein endothelial cells (HUVECs) proliferation and pro-inflammatory phenotype in response to subjects' serum stimulation were also evaluated. Results showed that the percentage of T and EPC subsets was reduced in SLE patients compared with HCs, with a marked increase of senescent CD28 cells among T subset. SLE disease activity index-2000 (SLEDAI-2K) was inversed related to T cells percentage. Furthermore, IL-8 serum levels were directly correlated with the percentage of T and inversely related to the CD28 T subsets. We indirectly evaluated the role of the T subset on the endothelium upon stimulation with serum from subjects with a low percentage of T CD3 cells in HUVECs. HUVECs displayed pro-inflammatory phenotype with up-regulation of mRNA for IL-6, intercellular adhesion molecule (ICAM)-1 and endothelial leukocyte adhesion molecule (ELAM)-1. Cell proliferation rate was directly related to IL-8 serum levels and EPC percentage. In highly selected young SLE patients without previous CV events, we found that the deterioration of T compartment is an early event in disease course, preceding the development of an overt cardiovascular disease and potentially mediated by SLE-specific mechanisms. The overcome of the CD28 subset exerts detrimental role over the T phenotype, where T could exert an anti-inflammatory effect on endothelial cells and might orchestrate IL-8 the function of EPCs, ultimately modulating endothelial proliferation rate.
系统性红斑狼疮 (SLE) 患者的心血管 (CV) 风险显著增加，尽管他们的循环血管生成 CD3CD31CXCR4 T 细胞 (T) 数量保持不变，T 细胞是促进受损内皮修复的 T 细胞亚群。这是由于具有免疫衰老特征的 T 亚群同时扩张所致，例如 CD28 的丧失。因此，本研究旨在阐明一群无先前心血管事件的年轻 SLE 患者中 T 亚群与内皮细胞之间的相互作用。招募了 20 名 SLE 女性患者和 10 名健康对照者 (HCs)。进行内皮祖细胞 (EPCs) 和 T 亚群的流式细胞术分析，并测量白细胞介素 (IL)-6、-8、基质金属蛋白酶 (MMP)-9 和干扰素 (IFN)-的血清水平。还评估了刺激受试者血清后 HUVECs 的增殖和促炎表型。结果显示，与 HCs 相比，SLE 患者的 T 细胞和 EPC 亚群的百分比减少，T 细胞亚群中衰老的 CD28 细胞明显增加。SLE 疾病活动指数-2000 (SLEDAI-2K) 与 T 细胞百分比呈负相关。此外，IL-8 血清水平与 T 细胞百分比呈直接相关，与 CD28 T 细胞亚群呈负相关。我们通过用 T CD3 细胞百分比低的受试者的血清刺激 HUVECs 来间接评估 T 亚群对内皮的作用。HUVECs 显示出促炎表型，IL-6、细胞间黏附分子 (ICAM)-1 和内皮白细胞黏附分子 (ELAM)-1 的 mRNA 表达上调。细胞增殖率与 IL-8 血清水平和 EPC 百分比呈直接相关。在没有先前 CV 事件的高度选择的年轻 SLE 患者中，我们发现 T 区室的恶化是疾病过程中的早期事件，早于明显心血管疾病的发生，并且可能由 SLE 特异性机制介导。克服 CD28 亚群对 T 表型发挥有害作用，其中 T 可以对内皮细胞发挥抗炎作用，并可能协调 IL-8 EPCs 的功能，最终调节内皮细胞增殖率。
