Quantitative increase in T regulatory cells enhances bone remodeling in osteogenesis imperfecta
In-Hong Kang,
Uday K. Baliga,
Shilpak Chatterjee,
Paramita Chakraborty,
Seungho Choi,
Nathan Buchweitz,
Hong Li,
Yongren Wu,
Hai Yao,
Shikhar Mehrotra,
Meenal Mehrotra
Affiliations
In-Hong Kang
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA; Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, 29425, USA
Uday K. Baliga
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA
Shilpak Chatterjee
Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA
Paramita Chakraborty
Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA
Seungho Choi
Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA
Nathan Buchweitz
Department of Orthopedics, Medical University of South Carolina, Charleston, SC 29425, USA; Department of Bioengineering, Clemson University, Clemson, SC 29634, USA; Clemson-MUSC Joint Bioengineering Program, South Carolina, USA
Hong Li
Depatment of Public Health Sciences, Medical University of South Carolina, Charleston, SC 29425, USA
Yongren Wu
Department of Orthopedics, Medical University of South Carolina, Charleston, SC 29425, USA; Department of Bioengineering, Clemson University, Clemson, SC 29634, USA; Clemson-MUSC Joint Bioengineering Program, South Carolina, USA
Hai Yao
Department of Orthopedics, Medical University of South Carolina, Charleston, SC 29425, USA; Department of Bioengineering, Clemson University, Clemson, SC 29634, USA; Clemson-MUSC Joint Bioengineering Program, South Carolina, USA; Department of Oral Health Sciences, Medical University of South Carolina, Charleston, SC 29425, USA
Shikhar Mehrotra
Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA
Meenal Mehrotra
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA; Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA; Department of Oral Health Sciences, Medical University of South Carolina, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA; Center for Oral Health Research, Medical University of South Carolina, Charleston, SC 29425, USA; Corresponding author
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.
