Murine mesenchymal stem cells suppress dendritic cell migration, maturation and antigen presentation

Abstract Mesenchymal stem cells (MSC) possess a wide range of immunosuppressive functions. Among these is the ability to inhibit CD4+ T cell proliferation. Dendritic cells (DC) play a role in initiating cell-mediated immunity; however, the immunosuppressive influence of MSC on professional antigen p...

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Bibliographic Details
Published in:Immunology letters 2008-01, Vol.115 (1), p.50-58
Main Authors: English, Karen, Barry, Frank P, Mahon, Bernard P
Format: Article
Language:English
Subjects:
Allergy and Immunology
Animals
Antigen Presentation
CCR7
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - metabolism
Cell Communication
Cell Differentiation
Cells, Cultured
Chemokine CCL19 - immunology
Chemokine CCL19 - metabolism
Chemotaxis
Dendritic cell
Dendritic Cells - cytology
Dendritic Cells - immunology
Dendritic Cells - metabolism
E-cadherin
Female
Immunity, Cellular
Immunosuppression
Mesenchymal stem cell
Mesenchymal Stromal Cells - immunology
Mesenchymal Stromal Cells - metabolism
Mice
Mice, Inbred BALB C
Tumor Necrosis Factor-alpha - metabolism
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Summary:Abstract Mesenchymal stem cells (MSC) possess a wide range of immunosuppressive functions. Among these is the ability to inhibit CD4+ T cell proliferation. Dendritic cells (DC) play a role in initiating cell-mediated immunity; however, the immunosuppressive influence of MSC on professional antigen presenting cells remains unclear. DC exposed to TNF-α and cultured with murine MSC failed to show regular upregulation of maturation markers. Similarly, the presence of MSC abrogated the capacity of ovalbumin-pulsed DC to support antigen specific CD4+ T cell proliferation, or for DC to display an MHC class II- peptide complex recognizable by specific antibody. Interestingly, culture of MSC with DC resulted in reduced expression of CCR7 by DC following stimulation. Likewise, DC matured in the presence of MSC, showed significantly less migration to CCL19. In contrast, murine MSC prevented loss of expression of the tissue anchoring protein E-cadherin by DC. Modulation of DC maturation and function was not permanent and could be restored after removal of MSC. These data demonstrate that MSC modulate the three cardinal features of DC maturation, providing the first demonstration of MSC interference with DC migration.
ISSN:0165-2478
1879-0542
DOI:10.1016/j.imlet.2007.10.002