Mesenchymal Stem Cells Suppress TNF-alpha Secretion from CD200 Receptor

Human mesenchymal stem cells (hMSCs) display immunosuppressive properties in vitro and the potential has also been transferred successfully to clinical trials for treatment of autoimmune diseases. OX-2 (CD200), a member of the immunoglobulin superfamily, is widely expressed in several tissues and has recently been found from hMSCs. The CD200 receptor (CD200R) occurs only in myeloid-lineage cells. The CD200-CD200R is involved in down-regulation of several immune cells, especially macrophages. The present study on 20 hMSC lines shows that the CD200 expression pattern varied from high (CD200Hi) to medium (CD200Me) and low (CD200Lo) in bone marrow-derived mesenchymal stem cell (BMMSC) lines, whereas umbilical cord blood derived mesenchymal stem cells (UCBMSCs) were constantly negative for CD200. The role of the CD200-CD200R axis in BMMSCs mediated immunosuppression was studied using THP-1 human macrophages. Interestingly, hMSCs showed greater inhibition of TNF-a secretion in co-cultures with IFN-c primed THP-1 macrophages when compared to LPS activated cells. The ability of CD200Hi BMMSCs to suppress TNF-a secretion from IFN-c stimulated THP-1 macrophages was significantly greater when compared to CD200Lo whereas UCBMSCs did not significantly reduce TNF-a secretion. The interference of CD200 binding to the CD200R by anti-CD200 antibody weakened the capability of BMMSCs to inhibit TNF-a secretion from IFN-c activated THP-1 macrophages. This study clearly demonstrated that the efficiency of BMMSCs to suppress TNF-a secretion of THP-1 macrophages was dependent on the type of stimulus. Moreover, the CD200-CD200r axis could have a previously unidentified role in the BMMSC mediated immunosuppression. Citation: Pietilä M, Lehtonen S, Tuovinen E, Lähteenmäki K, Laitinen S, et al. (2012) CD200 Positive Human Mesenchymal Stem Cells Suppress TNF-Alpha Secretion from CD200 Receptor Positive Macrophage-Like Cells. PLoS ONE 7(2): e31671. doi:10.1371/journal.pone.0031671 Editor: Rodrigo Alexandre Panepucci, Hemocentro de Ribeirão Preto, HC-FMRP-USP., Brazil Received September 27, 2011; Accepted January 11, 2012; Published February 20, 2012 Copyright: 2012 Pietilä et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was funded by the Academy of Finland (Grant: 122561) and by the Finnish Medical Association. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: [email protected]