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Front Immunol. 2018 Feb 1;9:95. doi: 10.3389/fimmu.2018.00095. eCollection 2018.

Senescent T-Cells Promote Bone Loss in Rheumatoid Arthritis.

Author information

1
Department of Rheumatology and Immunology, Medical University of Graz, Graz, Austria.
2
Department of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria.
3
Department of Internal Medicine VI, Innsbruck Medical University, Innsbruck, Austria.
4
Rheumatology Service, South Tyrolean Health Trust, Hospital Bruneck, Bruneck, Italy.

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.

KEYWORDS:

IL-15; T-lymphocyte; aging; osteoporosis; rheumatoid arthritis

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