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

被引：0
作者：
CY Luo
L Wang
C Sun
DJ Li
机构：
[1] Laboratory for Reproductive Immunology,Department of Obstetrics and Gynecology
[2] Hospital and Institute of Obstetrics and Gynecology,undefined
[3] Fudan University Shanghai Medical College,undefined
[4] Jiangsu Province Hospital,undefined
[5] the First Affiliated Hospital with Nanjing Medical University,undefined
[6] Affiliated Hospital,undefined
[7] Hainan Medical College,undefined
来源：
Cellular & Molecular Immunology | 2011年 / 8卷
关键词：
bone resorption; osteoclast; PMO; regulatory T cells;
D O I：
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学科分类号：
摘要：
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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页码：50 / 58
页数：8
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共 129 条
[1]  
Walsh MC(2006)Osteoimmunology: interplay between the immune system and bone metabolism Annu Rev Immunol 24 33-63
[2]  
Kim N(2000)Bone resorption by osteoclasts Science 289 1504-1508
[3]  
Kadono Y(2008)Estrogen deficiency increases osteoclastogenesis up-regulating T cells activity: a key mechanism in osteoporosis Bone 43 92-100
[4]  
Rho J(1993)Macrophage colony-stimulating factor is indispensable for both proliferation and differentiation of osteoclast progenitors J Clin Invest 91 257-263
[5]  
Lee SY(2002)RANKL and RANK: T cells, bone loss, and mammalian evolution Annu Rev Immunol 20 795-823
[6]  
Lorenzo J(2000)TNF-alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand J Clin Invest 106 1481-1488
[7]  
Teitelbaum SL(2007)Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems Nat Rev Immunol 7 292-304
[8]  
D'Amelio P(2005)The role of T-cell interleukin-17 in conducting destructive arthritis: lessons from animal models Arthritis Res Ther 7 29-37
[9]  
Grimaldi A(2000)Tumor necrosis factor alpha stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL–RANK interaction J Exp Med 191 275-286
[10]  
Di Bella S(2006)Cytokines regulating osteoclast formation and function Curr Opin Rheumatol 18 411-418
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