MicroRNA-30e-5p has an Integrated Role in the Regulation of the Innate Immune Response during Virus Infection and Systemic Lupus Erythematosus

MicroRNA-30e-5p has an Integrated Role in the Regulation of the Innate Immune Response during Virus Infection and Systemic Lupus Erythematosus
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DOI:
10.1016/j.isci.2020.101322
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发表时间:
2020-07-24
期刊:
影响因子:
5.8
通讯作者:
Kumar, Himanshu
Kumar, Himanshu
中科院分区:
综合性期刊2区
文献类型:
--
作者:
Mishra, Richa;Bhattacharya, Sanjana;Kumar, Himanshu

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先天免疫的精确调节对于发展适当的宿主免疫力以抵抗微生物感染和维持免疫稳态至关重要。 MicroRNA 是小型非编码 RNA,是多个基因的转录后调节因子,并充当蛋白质表达的变阻器。在这里,我们鉴定了由乙型肝炎病毒和其他病毒诱导的 microRNA-30e-5p,这些病毒充当先天免疫的主要调节因子。此外,聚乙二醇化干扰素治疗 HBV 患者的病毒减少也会减少 miRNA。此外,我们还展示了 miR-30e 对系统性红斑狼疮 (SLE) 患者和小鼠模型的免疫病理学影响。从机制上讲,miR-30e 靶向先天免疫信号传导的多个负调节因子并增强免疫反应。此外,SLE 患者和小鼠模型中 miR-30e 的隔离显着减少了 I 型干扰素和促炎细胞因子。总的来说,我们的研究证明了 miR-30e 在先天免疫中的新作用及其在传染性和自身免疫性疾病中的预后和治疗潜力。
Precise regulation of innate immunity is crucial for development of appropriate host immunity against microbial infections and maintenance of immune homeo-stasis. MicroRNAs are small non-coding RNAs, post-transcriptional regulator of multiple genes, and act as a rheostat for protein expression. Here, we identified microRNA-30e-5p induced by hepatitis B virus and other viruses that act as a mas-ter regulator for innate immunity. Moreover, pegylated interferons treatment of patients with HBV for viral reduction also reduces miRNA. Additionally, we have also shown the immuno-pathological effects of miR-30e in patients with systemic lupus erythematosus (SLE) and mouse model. Mechanistically, miR-30e targets multiple negative regulators of innate immune signaling and enhances immune re-sponses. Furthermore, sequestering of miR-30e in patients with SLE and mouse model significantly reduces type-I interferon and pro-inflammatory cytokines. Collectively, our study demonstrates the novel role of miR-30e in innate immunity and its prognostic and therapeutic potential in infectious and autoimmune diseases.