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Publication : Osteoclast-induced Foxp3+ CD8 T-cells limit bone loss in mice.

First Author  Buchwald ZS Year  2013
Journal  Bone Volume  56
Issue  1 Pages  163-73
PubMed ID  23756229 Mgi Jnum  J:317750
Mgi Id  MGI:6852207 Doi  10.1016/j.bone.2013.05.024
Citation  Buchwald ZS, et al. (2013) Osteoclast-induced Foxp3+ CD8 T-cells limit bone loss in mice. Bone 56(1):163-73
abstractText  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 (muCT) 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.
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