AUTHOR=Fessler Johannes , Husic Rusmir , Schwetz Verena , Lerchbaum Elisabeth , Aberer Felix , Fasching Patrizia , Ficjan Anja , Obermayer-Pietsch Barbara , Duftner Christina , Graninger Winfried , Stradner Martin Helmut , Dejaco Christian 

TITLE=Senescent T-Cells Promote Bone Loss in Rheumatoid Arthritis

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.00095

DOI=10.3389/fimmu.2018.00095

ISSN=1664-3224

ABSTRACT=<sec id="ST1"><title>Objective</title><p>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.</p></sec><sec id="ST2"><title>Methods</title><p>This includes a prospective study of consecutive patients with RA (<italic>n</italic> = 107), patients with primary osteopenia/-porosis (<italic>n</italic> = 75), and healthy individuals (<italic>n</italic> = 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<sup>+</sup>CD28<sup>−</sup> T-cells.</p></sec><sec id="ST3"><title>Results</title><p>Patients with osteopenia/-porosis yielded a higher prevalence of senescent CD4<sup>+</sup>CD28<sup>−</sup> 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<sup>+</sup>CD28<sup>−</sup> T-cells as compared to CD28<sup>+</sup> T-cells. Stimulation with interleukin-15 led to an up-regulation of RANKL expression, particularly on CD28<sup>−</sup> T-cells. CD4<sup>+</sup>CD28<sup>−</sup> T-cells induced osteoclastogenesis more efficiently than CD28<sup>+</sup> T-cells.</p></sec><sec id="ST4"><title>Conclusion</title><p>Our data indicate that senescent T-cells promote osteoclastogenesis more efficiently than conventional CD28<sup>+</sup> T-cells, which might contribute to the pathogenesis of systemic bone loss in RA and primary osteoporosis.</p></sec>