Bach2 in CD4+ T cells from SLE patients modulates B-cell differentiation and IgG production,European Journal of Immunology

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Bach2 in CD4+ T cells from SLE patients modulates B-cell differentiation and IgG production
European Journal of Immunology ( IF 4.5 ) Pub Date : 2023-02-13 , DOI: 10.1002/eji.202250109
Di Long ₁ , Bingyi Yang ₁ , Ming Yang ₁ , Feng Xiong ₁ , Xuejing Zhu ₂ , Yixin Tan ₁ , Haijing Wu ₁

Affiliation

T and B cells participate in the development of systemic lupus erythematosus (SLE). BTB and CNC homology 2 (Bach2) is an irreplaceable regulator in the T and B lineages that helps to maintain immune homeostasis. However, the function of Bach2 in the pathogenesis of SLE has not been studied in depth. Flow cytometry and qRT‒PCR were used to assess Bach2 levels, bisulfite sequencing PCR was used to measure the methylation level, and silencing by electroporation and stimulation with a cytokine concentration gradient were used to investigate the effect of Bach2 on T cells. Bach2 expression was elevated in the helper T-cell subsets (T follicular helper, Th1, Th2, Th17, and Treg cells) of SLE patients and negatively correlated with disease severity and autoantibody levels. CD4⁺ T cells from SLE patients had decreased methylation levels in the Bach2 promoter region. Silencing Bach2 in CD4⁺ T cells induced increases in the CD19⁺ B-cell count, plasmablasts, and secretion of IgG by prompting the secretion of cytokines. The activation signals CD3/CD28, IL-6, and IL-21 upregulated Bach2 expression in CD4⁺ T cells. The regulation of Bach2 by cytokines and T-cell activation signals in CD4⁺ T cells was shown to act on B cells and play a protective role against SLE.

中文翻译：

SLE 患者 CD4+ T 细胞中的 Bach2 调节 B 细胞分化和 IgG 产生

T 细胞和 B 细胞参与系统性红斑狼疮 (SLE) 的发展。BTB 和 CNC 同源性 2 (Bach2) 是 T 和 B 谱系中不可替代的调节因子，有助于维持免疫稳态。然而，Bach2 在 SLE 发病机制中的作用尚未得到深入研究。流式细胞术和 qRT-PCR 用于评估 Bach2 水平，亚硫酸氢盐测序 PCR 用于测量甲基化水平，电穿孔沉默和细胞因子浓度梯度刺激用于研究 Bach2 对 T 细胞的影响。Bach2 表达在 SLE 患者的辅助性 T 细胞亚群（T 滤泡辅助细胞、Th1、Th2、Th17 和 Treg 细胞）中升高，并且与疾病严重程度和自身抗体水平呈负相关。CD4 ⁺SLE 患者的 T 细胞 Bach2 启动子区域的甲基化水平降低。^{沉默 CD4 +} T 细胞中的 Bach2通过促进细胞因子的分泌，诱导 CD19 ⁺ B 细胞计数、浆母细胞和 IgG 分泌的增加。激活信号 CD3/CD28、IL-6 和 IL-21 上调 CD4 ⁺ T 细胞中的 Bach2 表达。^{CD4 +} T 细胞中细胞因子和 T 细胞激活信号对 Bach2 的调节显示作用于 B 细胞并发挥针对 SLE 的保护作用。

更新日期：2023-02-13

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