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

doi:10.1016/j.isci.2022.104818

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

iScience. 2022 Aug 5;25(9):104818. doi: 10.1016/j.isci.2022.104818. eCollection 2022 Sep 16.

Authors

In-Hong Kang^{1

2}, Uday K Baliga¹, Shilpak Chatterjee³, Paramita Chakraborty³, Seungho Choi³, Nathan Buchweitz^{4

5

6}, Hong Li⁷, Yongren Wu^{4

5

6}, Hai Yao^{4

5

6

8}, Shikhar Mehrotra^{3

9}, Meenal Mehrotra^{1

3

8

9

10}

Affiliations

¹ Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
² Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, 29425, USA.
³ Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.
⁴ Department of Orthopedics, Medical University of South Carolina, Charleston, SC 29425, USA.
⁵ Department of Bioengineering, Clemson University, Clemson, SC 29634, USA.
⁶ Clemson-MUSC Joint Bioengineering Program, South Carolina, USA.
⁷ Depatment of Public Health Sciences, Medical University of South Carolina, Charleston, SC 29425, USA.
⁸ Department of Oral Health Sciences, Medical University of South Carolina, Charleston, SC 29425, USA.
⁹ Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.
¹⁰ Center for Oral Health Research, Medical University of South Carolina, Charleston, SC 29425, USA.

Abstract

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.

Keywords: Cell biology; Components of the immune system; Immunology; Orthopedics.

Abstract

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