MicroRNA-130a Contributes to Type-2 Classical DC-activation in Sjögren's Syndrome by Targeting Mitogen- and

Ana P Lopes1,2, Joel A G van Roon1,2, Sofie L M Blokland1,2

  • 1Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.

Insights

Decreased microRNAs (miRNAs) like miR-130a in Sjögren's syndrome patients' dendritic cells correlate with increased inflammation. Targeting MSK1, regulated by miR-130a, offers a potential therapeutic strategy for this autoimmune disease.

Area of Science:

  • Immunology
  • Molecular Biology
  • Autoimmune Diseases

Background:

  • MicroRNAs (miRNAs) are key regulators of cell activation.
  • Circulating conventional type-2 dendritic cells (cDC2s) play a role in autoimmune diseases like primary Sjögren's syndrome (pSS).

Purpose of the Study:

  • To investigate the role of miRNAs in cDC2s from patients with pSS compared to healthy controls (HC).
  • To identify novel miRNA targets and therapeutic strategies for pSS.

Main Methods:

  • miRNA expression profiling in cDC2s from pSS patients and HC.
  • SILAC and flow cytometry to identify and validate miRNA targets and assess cytokine production.
  • Inhibition of MSK1 to evaluate its effect on cDC2 activation and cytokine release.

Main Results:

  • miR-130a and miR-708 expression were significantly decreased in pSS cDC2s.
  • MSK1 was identified as a novel target of miR-130a, and its inhibition reduced pro-inflammatory cytokine production (IL-12, TNF-α, IL-6).
  • pSS cDC2s exhibited higher MSK1 expression and increased IL-12 and TNF-α production.

Conclusions:

  • Decreased miR-130a and miR-708 in pSS cDC2s are associated with cell activation.
  • Targeting MSK1 presents a potential therapeutic avenue to modulate cDC2 activity in pSS.

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