Decreased expression of miR-146a and miR-155 contributes to an abnormal Treg phenotype in patients with rheumatoid arthritis
Q Zhou, S Haupt, JT Kreuzer, A Hammitzsch… - Annals of the …, 2015 - ard.bmj.com
Annals of the rheumatic diseases, 2015•ard.bmj.com
Objectives MicroRNAs (miRNAs) have been implicated in the pathogenesis of autoimmune
diseases, not least for their critical role in the regulation of regulatory T cell (Treg) function.
Deregulated expression of miR-146a and miR-155 has been associated with rheumatoid
arthritis (RA). We therefore investigated miR-146a and miR-155 expression in Tregs of
patients with RA and their possible impact on Treg function and disease activity. Methods
Expression of miR-146a and miR-155 was assessed in RA patients and controls. MiRNA …
diseases, not least for their critical role in the regulation of regulatory T cell (Treg) function.
Deregulated expression of miR-146a and miR-155 has been associated with rheumatoid
arthritis (RA). We therefore investigated miR-146a and miR-155 expression in Tregs of
patients with RA and their possible impact on Treg function and disease activity. Methods
Expression of miR-146a and miR-155 was assessed in RA patients and controls. MiRNA …
Objectives
MicroRNAs (miRNAs) have been implicated in the pathogenesis of autoimmune diseases, not least for their critical role in the regulation of regulatory T cell (Treg) function. Deregulated expression of miR-146a and miR-155 has been associated with rheumatoid arthritis (RA). We therefore investigated miR-146a and miR-155 expression in Tregs of patients with RA and their possible impact on Treg function and disease activity.
Methods
Expression of miR-146a and miR-155 was assessed in RA patients and controls. MiRNA expression was correlated with disease activity and expression of target genes. Interference with biological activity of miRNAs was evaluated in functional Treg assays.
Results
Diminished upregulation of miR-146a and miR-155 in response to T cell stimulation was found in Tregs of RA patients. Diminution of miR-146a expression was observed in particular in patients with active disease, and correlated with joint inflammation. In patients with active RA, Tregs demonstrated a pro-inflammatory phenotype characterised by inflammatory cytokine expression. This was due to an augmented expression and activation of signal transducer and activator transcription 1 (STAT1), a direct target of miR-146a.
Conclusions
Our results suggest that in RA miR-146a facilitates a pro-inflammatory phenotype of Tregs via increased STAT1 activation, and contributes thereby to RA pathogenesis.
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