Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Fessler, J; Husic, R; Schwetz, V; Lerchbaum, E; Aberer, F; Fasching, P; Ficjan, A; Obermayer-Pietsch, B; Duftner, C; Graninger, W; Stradner, MH; Dejaco, C.
Senescent T-Cells Promote Bone Loss in Rheumatoid Arthritis.
Front Immunol. 2018; 9:95
Doi: 10.3389/fimmu.2018.00095
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- Führende Autor*innen der Med Uni Graz
- Fessler Johannes
- Stradner Martin Helmut
- Co-Autor*innen der Med Uni Graz
- Aberer Felix
- Dejaco Christian
- Fasching Patrizia
- Ficjan Anja
- Graninger Winfried
- Husic Rusmir
- Lerchbaum Elisabeth
- Obermayer-Pietsch Barbara
- Theiler-Schwetz Verena
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Absorptiometry, Photon - administration & dosage
- Aged - administration & dosage
- Arthritis, Rheumatoid - complications, diagnosis, immunology, metabolism
- Biomarkers - administration & dosage
- Bone Density - administration & dosage
- Bone Resorption - etiology, metabolism
- CD4-Positive T-Lymphocytes - immunology, metabolism
- Cell Differentiation - administration & dosage
- Cellular Senescence - immunology
- Cytokines - metabolism
- Female - administration & dosage
- Humans - administration & dosage
- Immunophenotyping - administration & dosage
- Male - administration & dosage
- Middle Aged - administration & dosage
- Osteoclasts - metabolism
- RANK Ligand - metabolism
- T-Lymphocytes - immunology, metabolism
- Find related publications in this database (Keywords)
- T-lymphocyte
- rheumatoid arthritis
- osteoporosis
- aging
- IL-15