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Deregulation of microRNA expression in monocytes and CD4+ T lymphocytes from patients with axial spondyloarthritis

Authors: Fogel, Olivier; Bugge Tinggaard, Andreas; Fagny, Maud; Sigrist, Nelly; Roche, Elodie; Leclere, Laurence; Deleuze, Jean-François; +4 Authors

Deregulation of microRNA expression in monocytes and CD4+ T lymphocytes from patients with axial spondyloarthritis

Abstract

MicroRNAs (MiRs) play an important role in the pathogenesis of chronic inflammatory diseases. This study is the first to investigate miR expression profiles in purified CD4+ T lymphocytes and CD14+ monocytes from patients with axial spondyloarthritis (axSpA) using a high-throughput qPCR approach.A total of 81 axSpA patients fulfilling the 2009 ASAS classification criteria, and 55 controls were recruited from October 2014 to July 2017. CD14+ monocytes and CD4+ T lymphocytes were isolated from peripheral blood mononuclear cells. MiR expression was investigated by qPCR using the Exiqon Human MiRnome panel I analyzing 372 miRNAs. Differentially expressed miRNAs identified in the discovery cohort were validated in the replication cohort.We found a major difference in miR expression patterns between T lymphocytes and monocytes regardless of the patient or control status. Comparing disease-specific differentially expressed miRs, 13 miRs were found consistently deregulated in CD14+ cells in both cohorts with miR-361-3p, miR-223-3p, miR-484, and miR-16-5p being the most differentially expressed. In CD4+ T cells, 11 miRs were differentially expressed between patients and controls with miR-16-1-3p, miR-28-5p, miR-199a-5p, and miR-126-3p were the most strongly upregulated miRs among patients. These miRs are involved in disease relevant pathways such as inflammation, intestinal permeability or bone formation. Mir-146a-5p levels correlated inversely with the degree of inflammation in axSpA patients.We demonstrate a consistent deregulation of miRs in both monocytes and CD4+ T cells from axSpA patients, which could contribute to the pathophysiology of the disease with potential interest from a therapeutic perspective.

Keywords

CD4-Positive T-Lymphocytes, Male, MESH: Antirheumatic Agents, [SDV]Life Sciences [q-bio], Diseases of the musculoskeletal system, MESH: Monocytes, Monocytes, Cohort Studies, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Cohort Studies, Cells, Cultured, MESH: Cells, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, MESH: Middle Aged, Cultured, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Reverse Transcriptase Polymerase Chain Reaction, MESH: CD4-Positive T-Lymphocytes, Middle Aged, CD4+ T lymphocytes, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV] Life Sciences [q-bio], 3204 Immunology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, 1107 Immunology, Antirheumatic Agents, Epigenetics, Female, MiRNA, MESH: Spine, Research Article, Adult, MESH: Spondylarthritis, 610, 1117 Public Health and Health Services, MESH: Gene Expression Profiling, Spondyloarthritis, Spondylarthritis, Humans, MESH: Humans, CD4 T lymphocytes, Gene Expression Profiling, 3202 Clinical sciences, MESH: Adult, 1103 Clinical Sciences, MESH: Male, Spine, Arthritis & Rheumatology, MicroRNAs, RC925-935, MESH: MicroRNAs, MESH: Female

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
25
Top 10%
Average
Top 10%
Green
gold