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

被引:156
作者
Luo, C. Y. [1 ,2 ,3 ]
Wang, L. [1 ,2 ]
Sun, C. [1 ,2 ]
Li, D. J. [1 ,2 ,4 ]
机构
[1] Fudan Univ, Shanghai Med Coll, Lab Reprod Immunol, Hosp Obstet & Gynecol, Shanghai 200011, Peoples R China
[2] Fudan Univ, Shanghai Med Coll, Lab Reprod Immunol, Inst Obstet & Gynecol, Shanghai 200011, Peoples R China
[3] Nanjing Med Univ, Jiangsu Prov Hosp, Nanjing, Peoples R China
[4] Hainan Med Coll, Affiliated Hosp, Dept Obstet & Gynecol, Haikou, Peoples R China
基金
中国国家自然科学基金;
关键词
bone resorption; osteoclast; PMO; regulatory T cells; IMMUNE-SYSTEM; OSTEOIMMUNOLOGY; RANK; MECHANISMS; EXPRESSION;
D O I
10.1038/cmi.2010.54
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
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-beta 1) 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-beta 1 antibodies. Treatment of BMC and Treg cell cocultures with 17 beta-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-beta 1 expression. These data suggest that Treg cells suppress OC differentiation and bone resorption by secreting IL-10 and TGF-beta 1. E2 enhances the suppressive effects of Treg cells on OC differentiation and bone resorption by stimulating IL-10 and TGF-beta 1 secretion from these cells. Therefore, Treg cell-derived IL-10 and TGF-beta 1 are likely involved in the regulation of E2 on bone metabolism and represent potential therapeutic targets for the treatment of postmenopausal osteoporosis (PMO). Cellular & Molecular Immunology (2011) 8, 50-58; doi:10.1038/cmi.2010.54; published online 6 December 2010
引用
收藏
页码:50 / 58
页数:9
相关论文
共 32 条
[1]
Osteoimmunology - Bone versus immune system [J].
Arron, JR ;
Choi, Y .
NATURE, 2000, 408 (6812) :535-536
[2]
Mechanisms of T regulatory cell function [J].
Askenasy, Nadir ;
Kaminitz, Ayelet ;
Yarkoni, Shai .
AUTOIMMUNITY REVIEWS, 2008, 7 (05) :370-375
[3]
CD25brightCD4+ regulatory T cells accumulate in inflamed joints of patients with chronic rheumatic disease [J].
Cao, D ;
van Vollenhoven, R ;
Klareskog, L ;
Trollmo, C ;
Malmström, V .
ARTHRITIS RESEARCH & THERAPY, 2004, 6 (Suppl 1) :S14-S15
[4]
Estrogen deficiency increases osteoclastogenesis up-regulating T cells activity: A key mechanism in osteoporosis [J].
D'Amelio, Patrizia ;
Grimaldi, Anastasia ;
Di Bella, Stefania ;
Brianza, Stefano Z. M. ;
Cristofaro, Maria Angela ;
Tamone, Cristina ;
Giribaldi, Giuliana ;
Ulliers, Daniela ;
Pescarmona, Gian P. ;
Isaia, Giancarlo .
BONE, 2008, 43 (01) :92-100
[5]
Diminished forkhead box P3/CD25 double-positive T regulatory cells are associated with the increased nuclear factor-kB ligand (RANKL+) T cells in bone resorption lesion of periodontal disease [J].
Ernst, C. W. O. ;
Lee, J. E. ;
Nakanishi, T. ;
Karimbux, N. Y. ;
Rezende, T. M. B. ;
Stashenko, P. ;
Seki, M. ;
Taubman, M. A. ;
Kawai, T. .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2007, 148 (02) :271-280
[6]
Interleukin-10 inhibits osteoclastogenesis by reducing NFATcI expression and preventing its translocation to the nucleus [J].
Evans, Kathryn E. ;
Fox, Simon W. .
BMC CELL BIOLOGY, 2007, 8
[7]
Foxp3 Programs the Development and Function of CD4+CD25+ Regulatory T Cells (Reprinted from vol 4, pg 330-336, 2003) [J].
Fontenot, Jason D. ;
Gavin, Marc A. ;
Rudensky, Alexander Y. .
JOURNAL OF IMMUNOLOGY, 2017, 198 (03) :986-992
[8]
Transforming growth factor-β enables NFATc1 expression during osteoclastogenesis [J].
Fox, S. W. ;
Evans, K. E. ;
Lovibond, A. C. .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2008, 366 (01) :123-128
[9]
Control of regulatory T cell development by the transcription factor Foxp3 [J].
Hori, S ;
Nomura, T ;
Sakaguchi, S .
SCIENCE, 2003, 299 (5609) :1057-1061
[10]
Activated CD4+CD25+ regulatory T cells inhibit osteoclastogenesis and collagen-induced arthritis [J].
Kelchtermans, H. ;
Geboes, L. ;
Mitera, T. ;
Huskens, D. ;
Leclercq, G. ;
Matthys, P. .
ANNALS OF THE RHEUMATIC DISEASES, 2009, 68 (05) :744-750