Ligation of TLR2 and TLR4 on murine bone marrow-derived mesenchymal stem cells triggers differential effects on their immunosuppressive activity |
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| Authors: | Lei Junxia Wang Zhen Hui Dayang Yu Weihua Zhou Dunhua Xia Wenjie Chen Chun Zhang Qunzhou Wang Zhichong Zhang Qi Xiang Andy Peng |
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| Affiliation: | aCenter 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;bDepartment of Pathophysiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, PR China;cDepartment of Pediatrics, The Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510120, China;dGuangzhou Blood Center, Luyuan Road 31#, Guangzhou 510095, PR China;eCenter for Craniofacial Molecular Biology, School of Dentistry, University of Southern California, Los Angeles, CA, USA;fState Key Laboratory of Ophthalmology, Sun Yat-Sen University, Guangzhou 510060, PR China;gCell-Gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, PR China |
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| 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. |
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| Keywords: | Mesenchymal stem cells TLR2 TLR4 Allogeneic mixed lymphocytes reaction |
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