Regulatory effects of microRNAs on monocytic HLA‐DR surface expression

Decreased monocytic HLA‐DR expression is the most studied biomarker of immune competency in critically ill and autoimmune disease patients. However, the underlying regulatory mechanisms remain largely unknown. One probable HLA‐DR dysregulation is through microRNAs. The aim of this study was to investigate the effects of specific microRNAs on HLA‐DR expression in human monocytic cells. Four up‐ and four down‐HLA‐DR‐regulating microRNAs were identified, with hsa‐miR‐let‐7f‐2‐3p showing the most significant upregulation and hsa‐miR‐567 and hsa‐miR‐3972 downregulation. Anti‐inflammatory glucocorticoid medication Dexamethasone‐decreased HLA‐DR was significantly restored by hsa‐miR‐let‐7f‐2‐3p and hsa‐miR‐5693. Contrarily, proinflammatory cytokines IFN‐γ and TNF‐α‐increased HLA‐DR were significantly reversed by hsa‐miR‐567. Clinically, paired plasma samples from patients before and one day after cardiac surgery revealed up‐regulated expression of hsa‐miR‐5693, hsa‐miR‐567, and hsa‐miR‐3972, following the major surgical trauma. In silico approaches were applied for functional microRNA‐mRNA interaction prediction and candidate target genes were confirmed by qPCR analysis. In conclusion, novel monocytic HLA‐DR microRNA modulators were identified and validated in vitro. Moreover, both the interaction between the microRNAs and anti‐ and proinflammatory molecules and the up‐regulated microRNAs identified in cardiac surgery highlight the potential clinical relevance of our findings. HLA‐DR expression can be up‐ or downregulated by selected miRNAs in vitro. Moreover, miRNAs interact with major inflammatory modulators and co‐regulate the monocytic HLA‐DR expression. Altered levels of specific circulating extracellular miRNAs in plasma following major surgical trauma have shown promise as potential biomarkers and immune mediators in critical medicine.