Involvement of lncRNA IL21-AS1 in interleukin-2 and T follicular regulatory cell activation in systemic lupus erythematosus.

Involvement of lncRNA IL21-AS1 in interleukin-2 and T follicular regulatory cell activation in systemic lupus erythematosus.
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DOI:
10.1186/s13075-021-02682-w
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发表时间:
2021-12-11
影响因子:
4.9
通讯作者:
Tanaka Y
Tanaka Y
中科院分区:
医学2区
文献类型:
--
作者:
Hao H;Nakayamada S;Ohkubo N;Yamagata K;Zhang M;Shan Y;Iwata S;Zhang T;Tanaka Y

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位于IL 21反义RNA 1(IL 21-AS 1)的单核苷酸多态性(SNP)rs62324212已被确定为与系统性红斑狼疮(SLE)相关的遗传风险变异。本研究旨在探讨IL 21-AS 1在SLE患者T辅助细胞亚群和疾病活动性中的表达特点及其临床意义。rs62324212基因分型通过定量PCR使用等位基因辨别来确定。采用PCR和流式细胞术分析外周血单个核细胞中的基因表达和CD 4 + T细胞中的细胞表面标志物。探讨IL 21-AS 1、CD 4 + T细胞亚群与SLE疾病活动性的关系。Ensembl Genome Browser分析显示rs62324212(C>A)位于IL 21-AS 1的预测增强子区域。IL 21-AS 1表达于CD 4 + T、B细胞核,但在SLE患者中表达降低。IL-21-AS 1表达与IL-2 mRNA水平呈正相关,与活化的T滤泡调节细胞(Tfr)比例相关。此外,我们观察到SLE患者中IL 21-AS 1表达与疾病活动性呈显著负相关(n = 53,p < 0.05)。IL 21-AS 1通过参与IL-2介导的SLE中Tfr细胞的活化而对疾病活动性产生影响。因此,靶向IL 21-AS 1可能为SLE提供治疗方法。在线版本包含补充材料,可通过10.1186/s13075-021-02682-w获得。
The single nucleotide polymorphism (SNP) rs62324212, located in IL21 antisense RNA 1 (IL21-AS1), has been identified as a genetic risk variant associated with systemic lupus erythematosus (SLE). We aimed to probe the characteristics of IL21-AS1 and explore its clinical relevance focusing on T helper subsets and disease activity in patients with SLE. rs62324212 genotyping was determined using allelic discrimination by quantitative PCR. Gene expression in peripheral blood mononuclear cells and cell surface markers in CD4+ T cells were analyzed using PCR and flow cytometry. The association among IL21-AS1, CD4+ T cell subsets, and SLE disease activity was accessed. Ensembl Genome Browser analysis revealed that rs62324212 (C>A) was located in the predicting enhancer region of IL21-AS1. IL21-AS1 was expressed in the nucleus of CD4+ T and B cells, but its expression was decreased in patients with SLE. IL21-AS1 expression was positively correlated with mRNA levels of IL-2 but not IL-21, and it was associated with the proportion of activated T follicular regulatory (Tfr) cells. Furthermore, we observed a significant negative correlation between IL21-AS1 expression and disease activity in patients with SLE (n = 53, p < 0.05). IL21-AS1 has an effect on disease activity through an involvement of IL-2-mediated activation of Tfr cells in SLE. Thus, targeting the IL21-AS1 may provide therapeutic approaches for SLE. The online version contains supplementary material available at 10.1186/s13075-021-02682-w.
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