Ontology highlight
ABSTRACT: Objective
T-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.Methods
This 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.Results
Patients 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.Conclusion
Our 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.
SUBMITTER: Fessler J
PROVIDER: S-EPMC5810289 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
Frontiers in immunology 20180201
<h4>Objective</h4>T-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<sup>+</sup> T-cells is a hallmark feature of RA. Whether T-cell senescence is associated with bone loss in RA patients is elusive so far.<h4>Methods</h4>This includes a prospective study of consecutive patients with RA (<i>n</i> = 107), patients with primary osteopenia/-porosis (<i>n</i> = 75 ...[more]