Mesenchymal Stem Cells Inhibit Generation and Function of Both CD34+-Derived and Monocyte-Derived Dendritic Cells

Mesenchymal stem cells (MSCs) are not only able to evade the immune system, but they have also been demonstrated to exert profound immunosuppressive properties on T cell proliferation. However, their effect on the initiators of the immune response, the dendritic cells (DCs), are relatively unknown....

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Bibliographic Details
Published in:The Journal of immunology (1950) 2006-08, Vol.177 (4), p.2080-2087
Main Authors: Nauta, Alma J, Kruisselbrink, Alwine B, Lurvink, Ellie, Willemze, Roel, Fibbe, Willem E
Format: Article
Language:English
Subjects:
Adult
Antigens, CD34 - biosynthesis
Cell Differentiation - immunology
Cell Proliferation
Cells, Cultured
Dendritic Cells - cytology
Dendritic Cells - immunology
Dendritic Cells - metabolism
Fetus
Humans
Immunophenotyping
Mesenchymal Stem Cells - immunology
Monocytes - cytology
Monocytes - immunology
T-Lymphocytes - cytology
T-Lymphocytes - immunology
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Summary:Mesenchymal stem cells (MSCs) are not only able to evade the immune system, but they have also been demonstrated to exert profound immunosuppressive properties on T cell proliferation. However, their effect on the initiators of the immune response, the dendritic cells (DCs), are relatively unknown. In the present study, the effects of human MSCs on the differentiation and function of both CD34+ -derived DCs and monocyte-derived DCs were investigated. The presence of MSCs during differentiation blocked the differentiation of CD14+CD1a- precursors into dermal/interstitial DCs, without affecting the generation of CD1a+ Langerhans cells. In line with these observations, MSCs also completely prevented the generation of immature DCs from monocytes. The inhibitory effect of MSCs on DC differentiation was dose dependent and resulted in both phenotypical and functional modifications, as demonstrated by a reduced expression of costimulatory molecules and hampered capacity to stimulate naive T cell proliferation. The inhibitory effect of MSCs was mediated via soluble factors. Taken together, these data demonstrate that MSCs, next to the antiproliferative effect on T cells, have a profound inhibitory effect on the generation and function of both CD34+ -derived and monocyte-derived DCs, indicating that MSCs are able to modulate immune responses at multiple levels.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.177.4.2080