Regulatory effects of microRNAs on monocytic HLA-DR surface expression.

Folini, Anja; Zhang, Lan; Luedi, Markus M; Moolan-Vadackumchery, Robin; Matthiss, Lena; Hoffmann, Anneliese; Stüber, Frank; Huang, Melody Ying-Yu (2024). Regulatory effects of microRNAs on monocytic HLA-DR surface expression. European journal of immunology, 54(8), e2350756. Wiley-VCH 10.1002/eji.202350756

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic and Policlinic for Anaesthesiology and Pain Therapy > Partial clinic Insel
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Anästhesiologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Anästhesiologie

04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic and Policlinic for Anaesthesiology and Pain Therapy
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Folini, Anja Kristina, Zhang, Lan, Lüdi, Markus, Moolan-Vadackumchery, Robin, Matthiss, Lena Karina, Hoffmann, Anneliese, Stüber, Frank

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0014-2980

Publisher:

Wiley-VCH

Language:

English

Submitter:

Pubmed Import

Date Deposited:

24 May 2024 10:16

Last Modified:

01 Oct 2024 12:28

Publisher DOI:

10.1002/eji.202350756

PubMed ID:

38778505

Uncontrolled Keywords:

Cytokine Human leukocyte antigen (HLA) Immunosuppression MHC class II Monocyte microRNA (miRNA)

BORIS DOI:

10.48350/197044

URI:

https://boris.unibe.ch/id/eprint/197044

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