Quantitative increase in T regulatory cells enhances bone remodeling in osteogenesis imperfecta

Summary

Osteogenesis imperfecta (OI) is characterized by repeated bone fractures. Recent studies have shown that T lymphocytes and regulatory T cells (Tregs) regulate the functions of osteoclasts and osteoblasts, thus playing a role in bone turnover. We demonstrate an activated effector phenotype and higher secretion of pro-inflammatory cytokines, IFN-γ, and TNF-α in OI peripheral T cells as compared with wild-type (WT). Suppressive Tregs (spleen and thymus) were qualitatively similar, whereas there was a quantitative decrease in OI versus WT. Restoring Treg numbers by systemic transplantation in OI mice resulted in reduced T cell activation and effector cytokine secretion that correlated with significant improvements in tibial trabecular and cortical bone parameters and stiffness of femur, along with increased osteoblast mineralization and decreased osteoclast numbers. Therefore, Tregs can dampen the pro-inflammatory environment and enhance bone remodeling in OI mice. Thus, this study will be helpful in developing future autologous immunotherapy-based treatment modalities for OI.

Graphical abstract

Highlights

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  Activated T cell phenotype and higher secretion of pro-inflammatory cytokines in OI

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  Quantitative decrease in Tregs observed in OI mice compared with WT mice

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  Treg transplantation increases Tregs, reduces T cell activation and cytokine secretion

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  Treg transplantation produces improvements in bone remodeling and mechanical properties

Abstract

Orthopedics; Immunology ; Components of the immune system; Cell biology