Effect of Bone Morphogenetic Protein 6 on Immunomodulatory Functions of Salivary Gland-Derived Mesenchymal Stem Cells in Sjogren's Syndrome

被引：15

作者：

Xu, Junji ^{[1
,2
]}

Su, Yingying ^{[3
]}

Hu, Lei ^{[1
]}

Cain, Alexander ^{[2
]}

Gu, Yi ^{[4
]}

Liu, Bowen ^{[1
]}

Wu, Ruiqing ^{[3
]}

Wang, Songlin ^{[1
]}

Wang, Hao ^{[3
]}

机构：

[1] Capital Med Univ, Sch Stomatol, Beijing Key Lab Tooth Regenerat & Funct Reconstru, Tian Tan Xi Li 4, Beijing 100050, Peoples R China

[2] Natl Inst Dent & Craniofacial Res, Mucosal Immunol Sect, NIH, Bethesda, MD USA

[3] Capital Med Univ, Beijing Tiantan Hosp, Dept Stomatol, Tian Tan Xi Li 6, Beijing 100050, Peoples R China

[4] Capital Med Univ, Beijing Chaoyang Hosp, Dept Pediat, Beijing, Peoples R China

来源：

STEM CELLS AND DEVELOPMENT | 2018年 / 27卷 / 22期

基金：

美国国家科学基金会;

关键词：

bone morphogenetic protein 6; mesenchymal stem cells; Sjogren's syndrome; REGULATORY T-CELLS; PROSTAGLANDIN E-2; IMMUNOREGULATION; ID1; LYMPHOCYTES; DYSFUNCTION; EXPRESSION; INDUCTION; MECHANISM; RESPONSES;

D O I：

10.1089/scd.2017.0161

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Sjogren's syndrome (SS) is characterized by autoimmune activation and loss of function in the salivary glands. Recent studies reported that bone morphogenetic protein 6 (BMP6), which is a member of transforming growth factor beta (TGF-) superfamily, was highly expressed in SS patients. To investigate the role of BMP6 in SS, we treated the salivary gland-derived mesenchymal stem cells (SGMSCs) with BMP6 and found that BMP6 could impair immunomodulatory properties of normal SGMSCs by downregulating the Prostaglandin E2 synthase through DNA-binding protein inhibitor-1. Neutralizing the BMP6 could significantly restore the SGMSC's immunoregulatory function in vitro and delay the SS disease activity in vivo. In conclusion, BMP6 could not only affect the secreting function of epithelial cells in the salivary gland but also influence the immunomodulatory properties of SGMSCs, which may trigger or enhance the autoimmune reflection in SS.

引用

页码：1540 / 1548

页数：9

共 37 条

[1] Human mesenchymal stem cells modulate allogeneic immune cell responses
Aggarwal, S
Pittenger, MF
[J]. BLOOD, 2005, 105 (04) : 1815 - 1822
[2] Mesenchymal-Stem-Cell-Induced Immunoregulation Involves FAS-Ligand-/FAS-Mediated T Cell Apoptosis
Akiyama, Kentaro
Chen, Chider
Wang, DanDan
Xu, Xingtian
Qu, Cunye
Yamaza, Takayoshi
Cai, Tao
Chen, WanJun
Sun, Lingyun
Shi, Songtao
[J]. CELL STEM CELL, 2012, 10 (05) : 544 - 555
[3] BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism
Andriopoulos, Billy, Jr.
Corradini, Elena
Xia, Yin
Faasse, Sarah A.
Chen, Shanzhuo
Grgurevic, Lovorka
Knutson, Mitchell D.
Pietrangelo, Antonello
Vukicevic, Slobodan
Lin, Herbert Y.
Babitt, Jodie L.
[J]. NATURE GENETICS, 2009, 41 (04) : 482 - 487
[4] THE PROTEIN ID - A NEGATIVE REGULATOR OF HELIX-LOOP-HELIX DNA-BINDING PROTEINS
BENEZRA, R
DAVIS, RL
LOCKSHON, D
TURNER, DL
WEINTRAUB, H
[J]. CELL, 1990, 61 (01) : 49 - 59
[5] BETZ M, 1991, J IMMUNOL, V146, P108
[6] Immunoregulation by Mesenchymal Stem Cells: Biological Aspects and Clinical Applications
Castro-Manrreza, Marta E.
Montesinos, Juan J.
[J]. JOURNAL OF IMMUNOLOGY RESEARCH, 2015, 2015
[7] Immunoregulation by members of the TGFβ superfamily
Chen, WanJun
ten Dijke, Peter
[J]. NATURE REVIEWS IMMUNOLOGY, 2016, 16 (12) : 723 - 740
[8] Mesenchymal stem cells in immunoregulation
Chen, Xi
Armstrong, Marilyn Ann
Li, Gang
[J]. IMMUNOLOGY AND CELL BIOLOGY, 2006, 84 (05) : 413 - 421
[9] Cell contact, prostaglandin E2 and transforming growth factor beta 1 play non-redundant roles in human mesenchymal stem cell induction of CD4+CD25Highforkhead box P3+ regulatory T cells
English, K.
Ryan, J. M.
Tobin, L.
Murphy, M. J.
Barry, F. P.
Mahon, B. P.
[J]. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2009, 156 (01) : 149 - 160
[10] Mechanisms of mesenchymal stromal cell immunomodulation
English, Karen
[J]. IMMUNOLOGY AND CELL BIOLOGY, 2013, 91 (01) : 19 - 26

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