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

Zachary S. Buchwald, Jennifer R. Kiesel, Chang Yang, Richard DiPaolo, Deborah V. Novack, Rajeev Aurora

Research output: Contribution to journalArticle

23 Scopus citations

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.

Original languageEnglish
Pages (from-to)163-173
Number of pages11
JournalBone
Volume56
Issue number1
DOIs
StatePublished - Sep 1 2013

Keywords

  • FoxP3 CD8 T-cells
  • Negative feedback
  • Osteoclasts
  • Osteoimmunology
  • Osteoporosis

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    Buchwald, Z. S., Kiesel, J. R., Yang, C., DiPaolo, R., Novack, D. V., & Aurora, R. (2013). Osteoclast-induced Foxp3+ CD8 T-cells limit bone loss in mice. Bone, 56(1), 163-173. https://doi.org/10.1016/j.bone.2013.05.024