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

Olivier Fogel,Maud Fagny,Corinne Miceli-Richard,Maxime Dougados,Elodie Roche,Jean-François Deleuze,Laurence Leclere,Frederic Batteux,Nelly Sigrist,Jörg Tost,Andreas Bugge Tinggaard

doi:10.1186/s13075-019-1829-7

Abstract

BackgroundMicroRNAs (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.MethodsA 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.ResultsWe 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.ConclusionsWe 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.

Highlights

MicroRNAs (MiRs) play an important role in the pathogenesis of chronic inflammatory diseases
Monocytes/ macrophages are crucially involved in the disease pathogenesis notably through the HLA-B27-induced unfolded protein response (UPR) stress leading to the release of pro-inflammatory cytokines (IL-1α, TNF, IL-6, and IL-23) [12]
MiR expression in patients and controls is cell type specific One hundred sixty-three of the 193 miRs and 203 of the 223 miRs that could be reliably detected were significantly differentially expressed between CD4+ T lymphocytes and monocytes in the exploratory and replication cohort, respectively, after correction for multiple testing

Summary

Introduction

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. Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease that mainly affects the spine and sacroiliac joints in young adults. Genetic analyses identified the HLA-B27 and IL23R loci, whose proteins are present at the cell membrane of monocytes and T lymphocytes respectively, as the genetic factors most strongly associated with the disease [10, 11]. Monocytes/ macrophages are crucially involved in the disease pathogenesis notably through the HLA-B27-induced unfolded protein response (UPR) stress leading to the release of pro-inflammatory cytokines (IL-1α, TNF, IL-6, and IL-23) [12]. Adoptive transfer studies from disease-prone B27 transgenic rats to B27 nude rats demonstrated that CD4+ T cells were able to induce the disease [7]

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