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Monocyte MicroRNA Expression in Active Systemic Juvenile Idiopathic Arthritis Implicates MicroRNA-125a-5p in

Grant S Schulert1, Ndate Fall1, John B Harley1

  • 1Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

Arthritis & Rheumatology (Hoboken, N.J.)
|March 26, 2016
PubMed
Abstract

Insights

Systemic juvenile idiopathic arthritis (JIA) involves altered microRNA expression in monocytes. MicroRNA-125a-5p is significantly increased in active systemic JIA and drives M2b macrophage polarization, a key feature of the disease.

Area of Science:

  • Immunology
  • Molecular Biology
  • Pediatric Rheumatology

Background:

  • Systemic juvenile idiopathic arthritis (JIA) is a childhood inflammatory disease where monomyelocytoid cells are key effectors.
  • Monocytes in systemic JIA exhibit a distinct phenotype with M1 and M2 activation features.
  • MicroRNAs regulate monocyte polarization, but their role in systemic JIA remains understudied.

Purpose of the Study:

  • To systematically examine cellular microRNA expression profiles in monocytes from children with systemic JIA.
  • To investigate the role of microRNA-125a-5p (miR-125a-5p) in monocyte polarization in the context of systemic JIA.

Main Methods:

  • MicroRNA TaqMan arrays were employed to profile monocyte expression in systemic JIA patients.
  • In vitro studies utilized THP-1 cells and primary human monocytes to assess miR-125a-5p function.
  • Monocyte polarization was induced, and the effects of miR-125a-5p inhibition and overexpression were analyzed.

Main Results:

  • 110 microRNAs were differentially expressed in active systemic JIA monocytes, including those linked to rheumatoid arthritis and cytokine production.
  • miR-125a-5p was significantly upregulated in active systemic JIA monocytes, correlating with disease activity and systemic features.
  • In vitro, miR-125a-5p promoted M2b macrophage polarization, mimicking the phenotype observed in systemic JIA.

Conclusions:

  • Active systemic JIA is characterized by significant alterations in microRNA expression impacting monocyte function and polarization.
  • miR-125a-5p emerges as a critical regulator of immunoregulatory M2b macrophages in systemic JIA.
  • These findings highlight miR-125a-5p as a potential therapeutic target for systemic JIA.

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