BATF2 平衡 CADM 的 T 细胞介导的免疫应答与抗 MDA5 自身抗体。
BATF2 balances the T cell-mediated immune response of CADM with an anti-MDA5 autoantibody.
机构信息
Department of Rheumatology, Xiangya Hospital, Central South University, Changsha City, Hunan Province, China; Department of Pathophysiology, School of Basic Medicine Science, Central South University, Changsha City, Hunan Province, China; Sepsis Translational Medicine Key Lab of Hunan Province, Central South University, Changsha City, Hunan Province, China.
Department of Pathophysiology, School of Basic Medicine Science, Central South University, Changsha City, Hunan Province, China; Sepsis Translational Medicine Key Lab of Hunan Province, Central South University, Changsha City, Hunan Province, China.
出版信息
Biochem Biophys Res Commun. 2021 Apr 30;551:155-160. doi: 10.1016/j.bbrc.2021.02.128. Epub 2021 Mar 16.
OBJECTIVES
Clinically amyopathic dermatomyositis (CADM) is a subtype of dermatomyositis (DM) characterized by low-grade or absent muscle inflammation but frequent and rapidly progressive interstitial lung disease (RP-ILD) and skin ulcers with anti-melanoma differentiation-associated gene 5 (anti-MDA5) autoantibodies. Basic leucine zipper transcription factor ATF-like 2 (BATF2) is thought to function as an inhibitor of tumours and inflammation. Here, we aimed to investigate the roles of BATF2 in Th cell differentiation of CADM with an anti-MDA5 autoantibody (anti-MDA5 CADM).
METHODS
Naive CD4 T cells from human peripheral blood mononuclear cells (PBMCs) of healthy controls (HCs) were isolated and then cultured with IL-12, TGF-β or TGF-β plus IL-6 following anti-CD3 and anti-CD28 stimulations. The expression of BATF2 was measured by real-time PCR. The percentages of Th1, Th17 and Treg CD4 T cells were detected by flow cytometry. BATF2 knockdown of CD4 T cells was performed using small interfering RNAs (siRNAs).
RESULTS
The expression of BATF2 in PBMCs was higher in anti-MDA5 CADM patients than in healthy controls. The BATF2 mRNA expression was increased under Th1 and Treg polarization but decreased under Th17 polarization. Th17 cell activation-associated genes were possibly increased while Th1 and Treg cell differentiation-associated genes were inhibited by posttranscriptional gene silencing of BATF2 in CD4 T cells.
CONCLUSIONS
BATF2 promoted Th1 and Treg cell differentiation but suppressed Th17 cell activation in anti-MDA5 CADM.
目的
临床无肌病性皮肌炎（CADM）是皮肌炎（DM）的一种亚型，其特征为低度或无肌肉炎症，但频繁且快速进展的间质性肺病（RP-ILD）和皮肤溃疡，并伴有抗黑色素瘤分化相关基因 5（抗-MDA5）自身抗体。碱性亮氨酸拉链转录因子 ATF 样 2（BATF2）被认为是肿瘤和炎症的抑制剂。在此，我们旨在研究 BATF2 在抗-MDA5 自身抗体（抗-MDA5 CADM）所致 CADM 的 Th 细胞分化中的作用。
方法
从健康对照（HC）外周血单个核细胞（PBMC）中分离出幼稚 CD4 T 细胞，然后在抗-CD3 和抗-CD28 刺激下，用 IL-12、TGF-β 或 TGF-β 加 IL-6 进行培养。通过实时 PCR 测量 BATF2 的表达。通过流式细胞术检测 Th1、Th17 和 Treg CD4 T 细胞的百分比。使用小干扰 RNA（siRNA）对 CD4 T 细胞进行 BATF2 敲低。
结果
抗-MDA5 CADM 患者 PBMCs 中的 BATF2 表达高于健康对照。BATF2 mRNA 表达在 Th1 和 Treg 极化时增加，而在 Th17 极化时减少。在 CD4 T 细胞中，BATF2 的转录后基因沉默可能增加了 Th17 细胞激活相关基因的表达，而抑制了 Th1 和 Treg 细胞分化相关基因的表达。
结论
BATF2 促进了抗-MDA5 CADM 中的 Th1 和 Treg 细胞分化，但抑制了 Th17 细胞的激活。
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