Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Department for BioMedical Research, University of Bern, Bern, Switzerland.
Eur J Immunol. 2022 Sep;52(9):1452-1463. doi: 10.1002/eji.202149735. Epub 2022 Jun 9.
HLA-DR isotype is a MHC-II cell-surface receptor found on APCs and plays a key role in initiating immune responses. In severely immunocompromised patients with conditions like sepsis, the number of HLA-DR molecules expressed on leukocytes is considered to correlate with infectious complications and patients' probability of survival. The underlying regulatory mechanisms of HLA-DR expression remain largely unknown. One probable path to regulation is through microRNAs (miRNAs), which have been implicated as regulatory elements of both innate and adaptive immune system development and function. In our study, flow cytometry-based high-throughput miRNA screening was performed in a stable HLA-DR-expressing human melanoma cell line, MelJuSo, for either up- or downregulating miRNAs of the surface HLA-DR expression. By the end of the screening, the top ten upregulators and top five downregulators were identified, and both the HLA-DR protein and mRNA regulations were further verified and validated. In-silico approaches were applied for functional miRNA-mRNA interaction prediction. The potential underlying gene regulations of different miRNAs were proposed. Our results promote the study of miRNA-mediated HLA-DR regulation under both physiological and pathological conditions, and may pave the way for potential clinical applications.
HLA-DR 同种型是一种 MHC-II 细胞表面受体，存在于 APC 上，在启动免疫反应中起关键作用。在患有败血症等严重免疫功能低下的患者中，白细胞上表达的 HLA-DR 分子数量被认为与感染并发症和患者的生存率相关。HLA-DR 表达的潜在调节机制在很大程度上尚不清楚。一种可能的调节途径是通过 microRNAs（miRNAs），miRNAs 已被认为是先天和适应性免疫系统发育和功能的调节因子。在我们的研究中，在稳定表达 HLA-DR 的人黑色素瘤细胞系 MelJuSo 中进行了基于流式细胞术的高通量 miRNA 筛选，以上调或下调 HLA-DR 表面表达的 miRNA。筛选结束时，确定了前 10 个上调因子和前 5 个下调因子，并进一步验证和验证了 HLA-DR 蛋白和 mRNA 的调节。应用了计算方法进行 miRNA-mRNA 相互作用的功能预测。提出了不同 miRNA 的潜在潜在基因调节。我们的研究结果促进了生理和病理条件下 miRNA 介导的 HLA-DR 调节的研究，并可能为潜在的临床应用铺平道路。
