Priming of Toll-like receptor 4 pathway in mesenchymal stem cells increases expression of B cell activating factor.
Mesenchymal stem cells (MSCs) can be polarized into two distinct populations, MSC1 and MSC2, by activation of different Toll-like receptors (TLRs). TLR4-primed MSC1 expressed proinflammatory factors, whereas TLR3-primed MSC2 expressed suppressive factors. However, little is known about the function of TLRs on B lymphocyte-related immune modulation. In this study, we investigated the expression of B cell activating factor (BAFF), a member of the tumor necrosis factor ligand superfamily with notable stimulating activity on B cells, in human MSCs (hMSCs) and in murine MSCs (mMSCs) after activation of TLRs. BAFF was increasingly expressed in presence of TLR4 agonist (lipopolysaccharide, LPS), while TLR2 agonist (Zymosan) and TLR3-agonist (polyinocinic-polycytidykic acid, poly I:C) had no effect on BAFF expression. In addition, we demonstrated that signaling pathways of NF-κB, p38 MAPK, and JNK were involved in TLR4-primed BAFF expression. Our results suggested that TLR4 and downstream pathways in MSCs exert an important function in B lymphocyte-related immune regulation. Further defining a homogeneous population of MSCs should provide insight into MSC-based immune-modulating therapy.
Department of Hematology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Hao
H
Yan
Department of Hematology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Mengyao
M
Wu
Department of Hematology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Yan
Y
Yuan
John Hopkins University School of Medicine, Division of Hematology, Baltimore, MD 21205, United States.
Zack Z
ZZ
Wang
Department of Gynecology, Obstetrics & Gynecology Hospital, Fudan University, Shanghai 200011, China. Electronic address: jianghua@fudan.edu.cn.
Hua
H
Jiang
Department of Hematology, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: chentong@fudan.edu.cn.
Tong
T
Chen
D000328:Adult; D000818:Animals; D053264:B-Cell Activating Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism*; D015054:Zymosan / Q000494:pharmacology
D053264:B-Cell Activating Factor; D008070:Lipopolysaccharides; D016328:NF-kappa B; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C505719:TNFSF13B protein, human; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; C505720:Tnfsf13b protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D015054:Zymosan; D011070:Poly I-C
BAFF; LPS; Mesenchymal stem cell; Pro-inflammatory; TLR4