CD3(+)CD4(+)gp130(+) T Cells Are Associated With Worse Disease Activity in Systemic Lupus Erythematosus Patients.
CD3(+)CD4(+)gp130(+) T Cells Are Associated With Worse Disease Activity in Systemic Lupus Erythematosus Patients.
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DOI：
10.3389/fimmu.2021.675250
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发表时间：
2021
影响因子：
7.3
通讯作者：
Wong KK
中科院分区：
文献类型：
--
作者：
Mohd Shukri ND;Farah Izati A;Wan Ghazali WS;Che Hussin CM;Wong KK
IL-35、IL-12R、β-2和gp130受体参与了自身免疫性疾病的炎症病理生理过程。本研究检测了系统性红斑狼疮患者(n=50)和健康对照组(n=50)的血清IL-35水平和CD_3~+β~+、CD_3~+CD_4~+─、CD_3~+─~(─)淋巴细胞亚群表面IL-12R、CD2和gp130的水平。在公开可用的基因表达谱(GEP)数据集中，还检测了SLE患者CD4+T细胞中与gp130转录本(即IL6ST)表达相关的潜在T细胞亚群。在此，我们报告了系统性红斑狼疮患者血清IL-35水平显著高于健康对照组(p=0.038)，但与SLEDAI-2K评分无关。系统性红斑狼疮患者外周血中IL-12R、β~(2+)和gp130~+细胞所占比例与正常对照组无显著差异。SLEDAI-2K评分升高与β+T细胞中gp130+细胞比例增加呈正相关(r=0.425，p=0.002，q=0.016)，而与IL-12R CD2+细胞比例无关。对从系统性红斑狼疮患者(n=8；GSE4588)分离的CD_4~+T细胞的GEP数据集进行的基因集浓缩分析显示，IL_6ST的表达与CD_4~+T细胞相对于髓系细胞或B细胞上调的基因呈正相关(Q<；0.001)。在一个从SLE患者分离的独立的GEP数据集中(n=9；GSE1057)，在抗CD3刺激下，SLE患者中IL6ST的表达被诱导，而在这些SLE患者中，Treg、Tcm和CCR7+T细胞的基因集被与IL6ST表达高度相关的基因(n=92个基因；r>；0.75，IL6ST表达)显著丰富(Q<；0.05)。总之，CD3+CD4+T细胞亚群中的gp130信号可能有助于SLE患者疾病活动性的增加，它是一种有希望的抑制疾病的治疗靶点。
The receptors for IL-35, IL-12Rβ2 and gp130, have been implicated in the inflammatory pathophysiology of autoimmune diseases. In this study, we set out to investigate the serum IL-35 levels and the surface levels of IL-12Rβ2 and gp130 in CD3+CD4+, CD3+CD4─ and CD3─CD4─ lymphocyte subpopulations in systemic lupus erythematosus (SLE) patients (n=50) versus healthy controls (n=50). The potential T cell subsets associated with gp130 transcript (i.e. IL6ST) expression in CD4+ T cells of SLE patients was also examined in publicly-available gene expression profiling (GEP) datasets. Here, we report that serum IL-35 levels were significantly higher in SLE patients than healthy controls (p=0.038) but it was not associated with SLEDAI-2K scores. The proportions of IL-12Rβ2+ and gp130+ cells in SLE patients did not differ significantly with those of healthy controls in all lymphocyte subpopulations investigated. Essentially, higher SLEDAI-2K scores were positively correlated with increased proportion of gp130+ cells, but not IL-12Rβ2+ cells, on CD3+CD4+ T cells (r=0.425, p=0.002, q=0.016). Gene Set Enrichment Analysis (GSEA) of a GEP dataset of CD4+ T cells isolated from SLE patients (n=8; GSE4588) showed that IL6ST expression was positively associated with genes upregulated in CD4+ T cells vs myeloid or B cells (q<0.001). In an independent GEP dataset of CD4+ T cells isolated from SLE patients (n=9; GSE1057), IL6ST expression was induced upon anti-CD3 stimulation, and that Treg, TCM and CCR7+ T cells gene sets were significantly enriched (q<0.05) by genes highly correlated with IL6ST expression (n=92 genes; r>0.75 with IL6ST expression) upon anti-CD3 stimulation in these SLE patients. In conclusion, gp130 signaling in CD3+CD4+ T cell subsets may contribute to increased disease activity in SLE patients, and it represents a promising therapeutic target for inhibition in the disease.
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作者：
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通讯作者：
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