Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Department of Dermatology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku-gun, Ishikawa, 920-0293, Japan.
Sci Rep. 2021 Nov 30;11(1):23146. doi: 10.1038/s41598-021-02522-6.
Type I interferon (IFN) plays a crucial role in innate and adaptive immunity, and aberrant IFN responses are involved in systemic autoimmune diseases, such as systemic lupus erythematosus (SLE) and dermatomyositis (DM). Type I IFNs can be induced by transcribed retrotransposons. The regulation of retrotransposons and type I IFN and the downstream IFN pathways in SLE, DM, and autoimmune blistering disease (AIBD) were investigated. The gene expression levels of retrotransposons, including LINE-1, type I-III IFNs, and IFN-stimulated genes (ISGs) in peripheral blood cells from patients with DM (n = 24), SLE (n = 19), AIBD (n = 14) and healthy controls (HCs, n = 10) were assessed by quantitative polymerase chain reaction. Upregulation of retrotransposons and IFNs was detected in DM patient samples, as is characteristic, compared to HCs; however, ISGs were not uniformly upregulated. In contrast, retrotransposons and IFNs, except for type II IFN, such as IFN-γ, were not upregulated in SLE. In AIBD, only some retrotransposons and type I interferons were upregulated. The DM, SLE, and AIBD samples showed coordinated expression of retrotransposons and type I IFNs and distinct spectra of IFN signaling. A positive correlation between LINE-1 and IFN-β1 was also detected in human cell lines. These factors may participate in the development of these autoimmune diseases.
I 型干扰素 (IFN) 在先天和适应性免疫中发挥着至关重要的作用,异常的 IFN 反应与系统性自身免疫性疾病有关,如系统性红斑狼疮 (SLE) 和皮肌炎 (DM)。I 型 IFNs 可由转录的逆转录转座子诱导。研究了 SLE、DM 和自身免疫性水疱病 (AIBD) 中逆转录转座子、I 型 IFN 和 IFN 信号通路的调节。通过定量聚合酶链反应评估了 DM 患者(n=24)、SLE 患者(n=19)、AIBD 患者(n=14)和健康对照者(HCs,n=10)外周血细胞中的逆转录转座子基因表达水平,包括 LINE-1、I 型-III IFN 和 IFN 刺激基因 (ISGs)。与 HCs 相比,DM 患者样本中检测到逆转录转座子和 IFNs 的上调,这是特征性的;然而,ISGs 并未均匀上调。相比之下,SLE 中未上调逆转录转座子和除 II 型 IFN(如 IFN-γ)以外的 IFNs。在 AIBD 中,只有一些逆转录转座子和 I 型干扰素上调。DM、SLE 和 AIBD 样本显示出逆转录转座子和 I 型 IFNs 的协调表达,以及 IFN 信号的独特谱。在人类细胞系中还检测到 LINE-1 和 IFN-β1 之间的正相关。这些因素可能参与了这些自身免疫性疾病的发展。