Frontiers in Immunology (Feb 2018)

Senescent T-Cells Promote Bone Loss in Rheumatoid Arthritis

  • Johannes Fessler,
  • Rusmir Husic,
  • Verena Schwetz,
  • Elisabeth Lerchbaum,
  • Felix Aberer,
  • Patrizia Fasching,
  • Anja Ficjan,
  • Barbara Obermayer-Pietsch,
  • Christina Duftner,
  • Winfried Graninger,
  • Martin Helmut Stradner,
  • Christian Dejaco,
  • Christian Dejaco

DOI
https://doi.org/10.3389/fimmu.2018.00095
Journal volume & issue
Vol. 9

Abstract

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ObjectiveT-cells are critical players in the pathogenesis of osteoporosis in patients with rheumatoid arthritis (RA). Premature senescence of lymphocytes including the accumulation of senescent CD4+ T-cells is a hallmark feature of RA. Whether T-cell senescence is associated with bone loss in RA patients is elusive so far.MethodsThis includes a prospective study of consecutive patients with RA (n = 107), patients with primary osteopenia/-porosis (n = 75), and healthy individuals (n = 38). Bone mineral density (BMD) was determined by dual-energy X-ray absorptiometry scan. Flow cytometry, magnetic-associated cell sorting, and cell culture experiments were performed to analyze the pro-osteoclastic phenotype and the function of senescent CD4+CD28− T-cells.ResultsPatients with osteopenia/-porosis yielded a higher prevalence of senescent CD4+CD28− T-cells than individuals with normal BMD, in the RA, as well as in the non-RA cohort. Receptor activator of nuclear factor kappa-B ligand (RANKL) was expressed at higher levels on CD4+CD28− T-cells as compared to CD28+ T-cells. Stimulation with interleukin-15 led to an up-regulation of RANKL expression, particularly on CD28− T-cells. CD4+CD28− T-cells induced osteoclastogenesis more efficiently than CD28+ T-cells.ConclusionOur data indicate that senescent T-cells promote osteoclastogenesis more efficiently than conventional CD28+ T-cells, which might contribute to the pathogenesis of systemic bone loss in RA and primary osteoporosis.

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