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Estrogen enhances the functions of CD4+CD25+Foxp3+ regulatory T cells that suppress osteoclast differentiation and bone resorption in vitro

Cellular & Molecular Immunology volume 8, pages 50–58 (2011)Cite this article

Abstract

Cross-talk has been shown to occur between the immune system and bone metabolism pathways. In the present study, we investigated the impact of CD4+CD25+Foxp3+ regulatory T (Treg) cells on osteoclastogenesis and bone resorption. Treg cells that were isolated and purified from peripheral blood mononuclear cells (PBMCs) of healthy adults inhibited both the differentiation of osteoclasts (OCs) from human embryo bone marrow cells (BMCs) and the pit formation in a dose-dependent manner. In cell cocultures, the production levels of both interleukin-10 (IL-10) and transforming growth factor-beta 1 (TGF-β1) were proportionally upregulated as the ratio of Treg cells to BMCs was increased, and the inhibition of OC differentiation and bone resorption by Treg cells was completely reversed by anti-IL-10 and anti-TGF-β1 antibodies. Treatment of BMC and Treg cell cocultures with 17β-estradiol (E2) at concentrations between 10−7 and 10−9 mol/l suppressed OC differentiation and bone resorption more efficiently than it did in cultures of BMCs alone; this enhanced suppression occurred via the stimulation of Treg cell IL-10 and TGF-β1 expression. These data suggest that Treg cells suppress OC differentiation and bone resorption by secreting IL-10 and TGF-β1. E2 enhances the suppressive effects of Treg cells on OC differentiation and bone resorption by stimulating IL-10 and TGF-β1 secretion from these cells. Therefore, Treg cell-derived IL-10 and TGF-β1 are likely involved in the regulation of E2 on bone metabolism and represent potential therapeutic targets for the treatment of postmenopausal osteoporosis (PMO).

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Acknowledgements

We thank the volunteers for generously participating in this study. This work was supported by the National Key Research Program of China (No. 2006CB944007; to DJL), the National Natural Science Foundation of China (No. 30801502; to LW), the Shanghai Leading Academic Discipline Project B117 (to DJL) and the Program for Outstanding Medical Academic Leaders (to DJL).

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Authors and Affiliations

  1. Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, China

    CY Luo, L Wang, C Sun & DJ Li

  2. Jiangsu Province Hospital, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China

    CY Luo

  3. Department of Obstetrics and Gynecology, Affiliated Hospital, Hainan Medical College, Haikou, China

    DJ Li

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  1. CY Luo
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Correspondence to DJ Li.

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Luo, C., Wang, L., Sun, C. et al. Estrogen enhances the functions of CD4+CD25+Foxp3+ regulatory T cells that suppress osteoclast differentiation and bone resorption in vitro. Cell Mol Immunol 8, 50–58 (2011). https://doi.org/10.1038/cmi.2010.54

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