Expression and role of Toll-like receptors on human umbilical cord mesenchymal stromal cells.
OBJECTIVE
Toll-like receptors (TLRs) play an important role in innate and adaptive immunity by recognizing pathogen-associated molecular patterns (PAMPs).


METHODS
In the present study, we investigated the expression and role of TLRs on human umbilical cord mesenchymal stromal cells (UC-MSCs). The proliferation, differentiation and immunoregulatory activity of UC-MSCs primed with or without TLR ligands were determined.


RESULTS
At the RNA level, the expression of TLR2, 4, 6 and 9 was relatively higher than that of other TLRs. However, TLR3 and TLR4 expression were relatively higher at the protein level. UC-MSCs expressed functional TLRs by nuclear factor-κB activation and cytokine expression assay. Poly-inosinic acid:cytidylic acid [Poly(I:C)] stimulation inhibited the proliferation of UC-MSCs, but the ligand of other TLRs had no significant effect. Poly(I:C) stimulation enhanced the adipogenic differentiation capability of UC-MSCs, but lipopolysaccharide inhibited the adipogenic differentiation. Poly(I:C) and CpG-oligonucleotide promoted the immunosuppressive potentiality of UC-MSCs, accompanied with the phosphorylation of interferon regulatory factor 3 (IRF3) and increased expression of indoleamine 2,3-dioxygenase and interferon β, whereas activation of other TLR ligands (synthetic analog fibroblast-stimulating lipopeptide-1 and lipopolysaccharide) failed to affect the immunoregulatory activity of UC-MSCs.


CONCLUSIONS
Taken together, our data demonstrated that TLR activation influenced the function of UC-MSCs, which might have important implications in future efforts to explore the clinical potentials of UC-MSCs.
The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences, Tianjin, China.
Dandan
D
Chen
Fengxia
F
Ma
Shuxia
S
Xu
Shaoguang
S
Yang
Fang
F
Chen
Lijuan
L
Rong
Ying
Y
Chi
Qinjun
Q
Zhao
Shihong
S
Lu
Zhibo
Z
Han
Aiming
A
Pang
Zhongchao
Z
Han
D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D016899:Interferon-beta / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011070:Poly I-C / Q000494:pharmacology; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000096:biosynthesis / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000378:metabolism; D051216:Toll-Like Receptor 6 / Q000096:biosynthesis / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000096:biosynthesis / Q000378:metabolism; D051193:Toll-Like Receptors / Q000096:biosynthesis / Q000378:metabolism*; D014470:Umbilical Cord / Q000166:cytology*
C494232:IRF3 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D050838:Interferon Regulatory Factor-3; D008070:Lipopolysaccharides; D016328:NF-kappa B; C495342:TLR2 protein, human; C495344:TLR3 protein, human; C495345:TLR4 protein, human; C495368:TLR6 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D016899:Interferon-beta; D011070:Poly I-C