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. |