Implication of miR-126 and miR-139-5p in Plasmacytoid Dendritic Cell Dysregulation in Systemic Sclerosis

Eleni Chouri1,2, Maojie Wang3, Maarten R Hillen1,2

  • 1Center of Translational Immunology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands.

Insights

MicroRNAs (miRNAs) are altered in plasmacytoid dendritic cells (pDCs) of early-stage systemic sclerosis (SSc) patients. These changes may contribute to pDC activation in SSc pathogenesis.

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Plasmacytoid dendritic cells (pDCs) play a critical role in the pathogenesis of systemic sclerosis (SSc).
  • The molecular mechanisms underlying pDC dysregulation in early SSc remain incompletely understood.
  • MicroRNAs (miRNAs) are key regulators of gene expression and have been implicated in autoimmune diseases.

Purpose of the Study:

  • To investigate the role of miRNAs in the dysregulation of pDCs in patients with early-stage SSc.
  • To identify specific miRNAs and their targets involved in pDC activation in SSc.
  • To explore the potential of miRNA profiling as an early diagnostic marker for SSc.

Main Methods:

  • Isolation of circulating pDCs from two independent cohorts of SSc patients and healthy controls.
  • Comprehensive miRNA profiling and RNA-sequencing analysis of pDCs.
  • Proteomic analysis to identify direct miRNA targets at the protein level.
  • Toll-like receptor 9 (TLR9) stimulation assays on pDCs.

Main Results:

  • Significant differential expression of twelve and fifteen miRNAs in pDCs from SSc patients compared to controls in two cohorts.
  • Upregulation of miR-126 and miR-139-5p in both preclinical and definite SSc patients, correlating with type I interferon-responsive genes.
  • Identification of USP24 as a novel direct target of miR-139-5p, with inverse correlation in SSc patients and induction by TLR9 stimulation.

Conclusions:

  • The miRNA profile of pDCs is altered in early-stage SSc patients.
  • Specific miRNAs, such as miR-126 and miR-139-5p, may contribute to pDC activation in SSc.
  • These findings highlight the potential involvement of miRNAs in SSc pathogenesis and suggest their utility as early biomarkers.

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