title: Ligation of TLR2 and TLR4 on murine bone marrow-derived mesenchymal stem cells triggers differential effects on their immunosuppressive activity.
abstract: Mesenchymal stem cells (MSCs) have potent regulatory effects on immune and inflammatory responses. Recently the findings of functional TLR expression on MSC implicates these receptors in the function established for MSCs. Here we specially investigated the effects of TLR2, 4 ligation in mice MSC on migration, modulation of allogeneic mixed lymphocytes reaction (allo-MLR) and inducing Treg cells. We demonstrated that ligation of TLR2, but not TLR4, could significantly inhibit migration of MSC, impair MSC-mediated immunosuppression on allo-MLR, and reduce MSC-mediated expansion of CD4+CD25+Foxp3+ regulatory T cells. Compared with TLR4 activated MSCs and non-TLR activated MSC, TLR2 activation induced a relatively lower level of CXCL-10 mRNA and protein expressions which has been elucidated to act in concert with other soluble factor in MSC-mediated immunomodulation. These data indicate that TLR2 and TLR4 ligation had different effects on immunomodulatory capability of murine BMSCs, which should be considered in their use for treating inflammatory diseases.
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou 510080, PR China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Lei
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Dayang
authors.initials: D
authors.lastname: Hui
authors.forename: Weihua
authors.initials: W
authors.lastname: Yu
authors.forename: Dunhua
authors.initials: D
authors.lastname: Zhou
authors.forename: Wenjie
authors.initials: W
authors.lastname: Xia
authors.forename: Chun
authors.initials: C
authors.lastname: Chen
authors.forename: Qunzhou
authors.initials: Q
authors.lastname: Zhang
authors.forename: Zhichong
authors.initials: Z
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Andy Peng
authors.initials: AP
authors.lastname: Xiang
mesh_terms: D017667:Adipocytes / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D008074:Lipoproteins / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010011:Osteocytes / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000276:immunology* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000276:immunology* / Q000378:metabolism
chemical_list: D000950:Antigens, Ly; D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; D008074:Lipoproteins; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C069172:2,3-bis(palmitoyloxy)-2-propyl-1-palmitoylcysteine; D052247:Nitric Oxide Synthase Type II; D003545:Cysteine