Article Text

PDF
Extended report
FoxO3a involved in neutrophil and T cell survival is overexpressed in rheumatoid blood and synovial tissue
  1. Fanny Turrel-Davin1,2,
  2. Anne Tournadre1,2,3,
  3. Alexandre Pachot1,2,
  4. Béatrice Arnaud1,2,
  5. Marie-Angélique Cazalis1,2,
  6. Bruno Mougin1,2,
  7. Pierre Miossec1,2
  1. 1Joint Unit Hospices Civils de Lyon – bioMérieux, Hôpital Edouard Herriot, Lyon, France
  2. 2Immunogenomics and Inflammation Research Unit, University of Lyon, Lyon, France
  3. 3CHU Clermont-Ferrand, Department of Rheumatology, Clermont-Ferrand, France
  1. Correspondence to Pierre Miossec, Clinical Immunology Unit, Department of Immunology and Rheumatology, Hôpital Edouard Herriot, 5, place d'Arsonval, 69003 Lyon, France; miossec{at}univ-lyon1.fr

Abstract

Objective FoxO3a is a transcriptional factor implicated in cell cycle regulation and apoptosis. Since rheumatoid arthritis (RA) is associated with apoptosis defects, the expression level, regulation and phosphorylation status of FoxO3a was investigated in blood and synovium from patients with RA.

Methods In microarray experiments, an overexpression of FoxO3a mRNA was observed in blood from patients with RA compared with healthy controls. FoxO3a mRNA expression was quantified in polymorphonuclear cells (PMNs) and peripheral blood mononuclear cells from patients with RA by qRT-PCR. Total FoxO3a and phosphorylated FoxO3a (pFoxO3a) protein expression was analysed in blood leucocytes from patients with RA versus controls and in synovium from patients with RA versus patients with osteoarthritis (OA) by immunostaining.

Results FoxO3a mRNA and protein expression levels were increased in blood from patients with RA compared with controls. FoxO3a overexpression was primarily observed in PMNs. In synovium from patients with RA, both total and inactive phosphorylated FoxO3a proteins were detected. FoxO3a was detected primarily in the sublining T lymphocytes of synovium from patients with RA compared with the lining layer tissue from patients with RA and OA, underlying a role for FoxO3a proteins in inflammation in RA.

Conclusion The overexpression of FoxO3a in blood from patients with RA, particularly in PMNs, suggests a potential role for this gene in the pathogenesis of RA through increased survival of blood PMNs. In synovium from patients with RA, FoxO3a mainly detected in inflammatory aggregates may also regulate the chronic survival of T lymphocytes.

Statistics from Altmetric.com

Footnotes

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval The protocol was approved by the local ethical committee and all patients gave their informed consent.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.