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THU0269 A Multitude of Downregulated miRNAs in Plasmacytoid Dcs of Sjögren's Syndrome Patients Indicates Numerous Dysregulated Signalling Pathways
  1. M.R. Hillen,
  2. E. Chouri,
  3. S.L. Blokland,
  4. A.A. Kruize,
  5. F.P. Lafeber,
  6. M. Rossato,
  7. J.A. van Roon,
  8. T.R. Radstake
  1. Rheumatology & Clinical Immunology, UMC Utrecht, Utrecht, Netherlands

Abstract

Background Plasmacytoid dendritic cells (pDCs) are indicated to be key players in the pathogenesis of primary Sjögren's syndrome (pSS) and important producers of type-1 interferon (IFN). This is based on their increased presence in pSS salivary glands, potential role in experimental animal models and the presence of an IFN signature in pSS patients, which is associated with disease activity measures. MicroRNAs (miRNA) are key regulators of cellular function and may play a pivotal role in pDC function.

Objectives To unravel the role of miRNAs in pDCs of pSS patients, we investigated the expression of miRNA in these cells in pSS patients.

Methods Two independent cohorts (discovery and validation) were established including a total of 30 pSS patients. 15 healthy controls (HC) were included as control group and divided over the two cohorts. CD304-expressing pDCs were isolated from peripheral blood using MACS and profiling of 758 miRNA was performed using the OpenArray platform in the donors included in the discovery cohort. miRNAs found to be differentially expressed in the discovery cohort were subsequently measured in an independent validation cohort. Experimentally supported targets of validated miRNAs were used to perform pathway enrichment.

Results A total of 24 miRNAs were significantly downregulated in pSS patients versus HC in the discovery cohort (all p<0.05 and >2log fold difference). 15 miRNAs were selected to be measured in the validation cohort, ten of these miRNAs were subsequently validated (p<0.05). Pathway enrichment indicated that these miRNAs are mainly involved in regulation of growth factor signalling and cell cycle (FDR corrected, p<0.05), including MTOR and PI-3K pathways. We are currently studying the involvement of these miRNAs in pDC function by linking miRNA expression to RNA sequencing data and in vitro functional assays.

Conclusions We here for the first time show differential expression of miRNAs in isolated pDCs of pSS patients. Considering the strong potential of miRNAs in regulation of cell function, these data suggest a significant contribution to pDC function. Further analysis of the pathways in which these miRNAs are involved will expand our understanding on the role of pDCs in pSS.

Disclosure of Interest None declared

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