Title |
Senescent T-Cells Promote Bone Loss in Rheumatoid Arthritis
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Published in |
Frontiers in immunology, February 2018
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DOI | 10.3389/fimmu.2018.00095 |
Pubmed ID | |
Authors |
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 |
Abstract |
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. 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. 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. 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. |
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United States | 1 | 13% |
United Kingdom | 1 | 13% |
Sri Lanka | 1 | 13% |
Unknown | 4 | 50% |
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Members of the public | 5 | 63% |
Scientists | 3 | 38% |
Mendeley readers
Geographical breakdown
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Unknown | 66 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Bachelor | 9 | 14% |
Student > Master | 8 | 12% |
Researcher | 7 | 11% |
Student > Doctoral Student | 6 | 9% |
Student > Ph. D. Student | 6 | 9% |
Other | 12 | 18% |
Unknown | 18 | 27% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 11 | 17% |
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Immunology and Microbiology | 7 | 11% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 5% |
Other | 6 | 9% |
Unknown | 20 | 30% |