Autor: |
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 |
Jazyk: |
angličtina |
Rok vydání: |
2018 |
Předmět: |
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Zdroj: |
Frontiers in Immunology, Vol 9 (2018) |
Druh dokumentu: |
article |
ISSN: |
1664-3224 |
DOI: |
10.3389/fimmu.2018.00095 |
Popis: |
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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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