Decreased Dicer expression is linked to increased expression of co-stimulatory molecule CD80 on B cells in multiple sclerosis

Mult Scler. 2015 Aug;21(9):1131-8. doi: 10.1177/1352458514560923. Epub 2014 Dec 5.

Abstract

Background: Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system. B cells have been strongly implicated in disease pathogenesis based on clinical trials with B-cell ablation. There is a growing body of evidence linking microRNAs with regulation of the immune system. Dicer, a key enzyme involved in microRNA biogenesis, is necessary for normal B-cell function.

Objective: We aimed to determine whether Dicer expression is impaired in B cells and is linked to increased expression co-stimulatory molecules in patients with MS.

Methods: B cells were separated from blood samples of MS patients and healthy subjects. Expression of Dicer and co-stimulatory molecules CD80 and CD86 was tested. The effect of Dicer modulation on CD80 and CD86 expression in B cells was studied.

Results: Dicer expression was decreased in B cells but not in monocytes of patients with MS compared with healthy subjects. CD80 and CD86 expression was increased on B cells of MS patients compared with healthy subjects. Inhibition of Dicer expression in B cells by small interfering RNA led to increased expression of CD80.

Conclusion: Dicer expression is decreased and is mechanistically linked to increased expression of co-stimulatory molecule CD80 in B cells of patients with MS. This may contribute to activation of immune responses in MS.

Keywords: B cells; CD80; Dicer; Multiple sclerosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • B7-1 Antigen / biosynthesis*
  • B7-1 Antigen / immunology
  • B7-2 Antigen / biosynthesis
  • B7-2 Antigen / immunology
  • Blotting, Western
  • DEAD-box RNA Helicases / biosynthesis*
  • Demyelinating Diseases / immunology
  • Female
  • Flow Cytometry
  • Gene Expression Regulation / immunology*
  • Humans
  • Male
  • Multiple Sclerosis, Relapsing-Remitting / immunology*
  • Real-Time Polymerase Chain Reaction
  • Ribonuclease III / biosynthesis*

Substances

  • B7-1 Antigen
  • B7-2 Antigen
  • CD86 protein, human
  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases