SF Treg cells transcribing high levels of Bcl-2 and microRNA-21 demonstrate limited apoptosis in RA

Rheumatology (Oxford). 2015 May;54(5):950-8. doi: 10.1093/rheumatology/keu407. Epub 2014 Oct 21.

Abstract

Objective: The aim of this study was to investigate the turnover of Treg cells in the SF of RA patients.

Methods: Treg cells were enumerated in peripheral blood and SF of RA patients and analysed by flow cytometry for expression of the proliferation marker Ki-67 and binding of the apoptosis marker annexin V. Sorted Treg cells of RA patients were analysed for expression of anti-apoptotic regulators Bcl-2 and microRNA-21 (miR-21) by RT-PCR.

Results: Treg cells displaying a memory phenotype were abundant in the SF of RA patients. SF Treg cells more frequently expressed the proliferation marker Ki-67 than conventional T cells. Only few SF Treg cells were apoptotic, as indicated by limited annexin V staining of these cells. SF Treg cells displayed high transcription levels of Bcl-2 and miR-21 in comparison with SF conventional T cells and peripheral blood Treg cells.

Conclusion: Treg cells with a memory phenotype accumulate in the SF of RA patients. These Treg cells have a high proliferative activity and demonstrate little apoptosis. The latter finding could be explained by high transcription of Bcl-2 and miR-21 in SF Treg cells.

Keywords: Bcl-2; apoptosis; cell proliferation; miR-21; microRNA; regulatory T cell; rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Annexin A5 / metabolism
  • Apoptosis / physiology*
  • Arthritis, Rheumatoid / metabolism*
  • Arthritis, Rheumatoid / pathology*
  • Arthritis, Rheumatoid / physiopathology
  • Biomarkers / metabolism
  • Case-Control Studies
  • Cell Proliferation / physiology
  • Female
  • Humans
  • Ki-67 Antigen / metabolism
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Phenotype
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Synovial Fluid / cytology*
  • T-Lymphocytes, Regulatory / metabolism*
  • T-Lymphocytes, Regulatory / pathology

Substances

  • Annexin A5
  • Biomarkers
  • Ki-67 Antigen
  • MIRN21 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2