title: Osteoclast-induced Foxp3+ CD8 T-cells limit bone loss in mice.
abstract: Osteoimmunology is the crosstalk between the skeletal and immune systems. We have previously shown in vitro that osteoclasts (OC) crosspresent antigens to induce FoxP3 in CD8 T-cells (OC-iTc(REG)), which then suppress osteoclast activity. Here we assessed the ability of OC-iTc(REG) to limit bone resorption in vivo. Mice lacking CD8 T-cells lose more bone in response to RANKL (Tnfsf11) administration. Using adoptive transfer experiments we demonstrate that FoxP3(+) CD8 T-cells limit bone loss by RANKL administration. In ovariectomized mice, a murine model of postmenopausal osteoporosis, OC-iTc(REG) limited bone loss and increased bone density as assessed by serum markers, micro computed tomography (μCT) and histomorphometry. Indeed, OC-iTc(REG)-treated ovariectomized mice had decreased levels of effector T-cells in the bone marrow compared to untreated mice, and increased bone formation rates relative to bisphosphonate-treated mice. Our results provide the first in vivo evidence that OC-iTc(REG) have anti-resorptive activity and repress the immune system, thus extending the purview of osteoimmunology.
authors.affiliation: Dept. of Molecular Microbiology and Immunology, St. Louis University, Saint Louis, MO 63104, USA.
authors.forename: Zachary S
authors.initials: ZS
authors.lastname: Buchwald
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Kiesel
authors.forename: Chang
authors.initials: C
authors.lastname: Yang
authors.forename: Richard
authors.initials: R
authors.lastname: DiPaolo
authors.forename: Deborah V
authors.initials: DV
authors.lastname: Novack
authors.forename: Rajeev
authors.initials: R
authors.lastname: Aurora
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000276:immunology* / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002452:Cell Count; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010012:Osteogenesis / Q000187:drug effects; D010052:Ovariectomy; D053245:RANK Ligand / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053245:RANK Ligand
keywords: FoxP3 CD8 T-cells; Negative feedback; Osteoclasts; Osteoimmunology; Osteoporosis