Osteoclast-induced Foxp3+ CD8 T-cells limit bone loss in mice
Bone, 2013•Elsevier
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 …
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 …
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-iTcREG), which then suppress osteoclast activity. Here we assessed the ability of OC-iTcREG 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-iTcREG limited bone loss and increased bone density as assessed by serum markers, micro computed tomography (μCT) and histomorphometry. Indeed, OC-iTcREG—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-iTcREG have anti-resorptive activity and repress the immune system, thus extending the purview of osteoimmunology.
Elsevier