title: CD200 positive human mesenchymal stem cells suppress TNF-alpha secretion from CD200 receptor positive macrophage-like cells.
abstract: 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-α secretion in co-cultures with IFN-γ primed THP-1 macrophages when compared to LPS activated cells. The ability of CD200Hi BMMSCs to suppress TNF-α secretion from IFN-γ stimulated THP-1 macrophages was significantly greater when compared to CD200Lo whereas UCBMSCs did not significantly reduce TNF-α secretion. The interference of CD200 binding to the CD200R by anti-CD200 antibody weakened the capability of BMMSCs to inhibit TNF-α secretion from IFN-γ activated THP-1 macrophages. This study clearly demonstrated that the efficiency of BMMSCs to suppress TNF-α 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.
authors.affiliation: Institute of Biomedicine, Department of Anatomy and Cell Biology, University of Oulu, Oulu, Finland. mika.pietila@aalto.fi
authors.forename: Mika
authors.initials: M
authors.lastname: Pietilä
authors.forename: Siri
authors.initials: S
authors.lastname: Lehtonen
authors.forename: Elina
authors.initials: E
authors.lastname: Tuovinen
authors.forename: Kaarina
authors.initials: K
authors.lastname: Lähteenmäki
authors.forename: Saara
authors.initials: S
authors.lastname: Laitinen
authors.forename: Hannu-Ville
authors.initials: HV
authors.lastname: Leskelä
authors.forename: Antti
authors.initials: A
authors.lastname: Nätynki
authors.forename: Juha
authors.initials: J
authors.lastname: Pesälä
authors.forename: Katrina
authors.initials: K
authors.lastname: Nordström
authors.forename: Petri
authors.initials: P
authors.lastname: Lehenkari
mesh_terms: D000906:Antibodies / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D018920:Coculture Techniques; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D064446:Orexin Receptors; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D000954:Antigens, Surface; C477337:CD200R1 protein, human; D064446:Orexin Receptors; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; C042739:antigens, CD200