Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2-dependent regulatory dendritic cell population.
Mesenchymal stem cells (MSCs), in addition to their multilineage differentiation, exert immunomodulatory effects on immune cells, even dendritic cells (DCs). However, whether they influence the destiny of full mature DCs (maDCs) remains controversial. Here we report that MSCs vigorously promote proliferation of maDCs, significantly reduce their expression of Ia, CD11c, CD80, CD86, and CD40 while increasing CD11b expression. Interestingly, though these phenotypes clearly suggest their skew to immature status, bacterial lipopolysaccharide (LPS) stimulation could not reverse this trend. Moreover, high endocytosic capacity, low immunogenicity, and strong immunoregulatory function of MSC-treated maDCs (MSC-DCs) were also observed. Furthermore we found that MSCs, partly via cell-cell contact, drive maDCs to differentiate into a novel Jagged-2-dependent regulatory DC population and escape their apoptotic fate. These results further support the role of MSCs in preventing rejection in organ transplantation and treatment of autoimmune disease.
Zhang
Bin
B
Center of Excellence in Tissue Engineering, Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.
Liu
Rui
R
Shi
Dan
D
Liu
Xingxia
X
Chen
Yuan
Y
Dou
Xiaowei
X
Zhu
Xishan
X
Lu
Chunhua
C
Liang
Wei
W
Liao
Lianming
L
Zenke
Martin
M
Zhao
Robert C H
RC
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D051940:B7-2 Antigen / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D016130:Immunophenotyping; D007249:Inflammation / Q000276:immunology; D000072101:Jagged-2 Protein; D007959:Lymphocyte Culture Test, Mixed; D008565:Membrane Proteins / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
D051940:B7-2 Antigen; D039481:CD11b Antigen; D039521:CD11c Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; C490503:Jag2 protein, mouse; D000072101:Jagged-2 Protein; D008565:Membrane Proteins; D049452:Green Fluorescent Proteins