Mesenchymal stem cells impair in vivo T-cell priming by dendritic cells
| Autor: | Michela Massollo, Silvia Morbelli, Cecilia Marini, Antonio Uccelli, Sabrina Chiesa, Elisabetta Traggiai, Sara Morando, Soraya Tabera Bartolomé, Arinna Bertoni, Gianmario Sambuceti, Francesco Frassoni |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
CD4-Positive T-Lymphocytes
Stromal cell T-Lymphocytes Cellular differentiation T cell Antigen presentation Gene Expression Priming (immunology) Mice Transgenic CD8-Positive T-Lymphocytes Biology Inbred C57BL Animals Antigen Presentation CD4-Positive T-Lymphocytes immunology CD8-Positive T-Lymphocytes immunology Cell Differentiation immunology Cell Movement immunology Coculture Techniques Cytokines genetics Dendritic Cells cytology/immunology/physiology/transplantation Gene Expression Lymph Nodes cytology/immunology Mesenchymal Stem Cells immunology Mice Mice Inbred BALB C Mice Inbred C57BL Mice Transgenic Signal Transduction immunology T-Lymphocytes immunology Toll-Like Receptor 4 genetics/immunology Transgenic immunology Mice Cell Movement cytology/immunology medicine Animals genetics cytology/immunology/physiology/transplantation Progenitor cell Inbred BALB C Mice Inbred BALB C Antigen Presentation Multidisciplinary Mesenchymal stem cell Cell Differentiation Mesenchymal Stem Cells Dendritic Cells Biological Sciences Molecular biology Coculture Techniques Cell biology Mice Inbred C57BL Toll-Like Receptor 4 medicine.anatomical_structure Cytokines Lymph Nodes CD8 Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences. 108:17384-17389 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Dendritic cells (DC) are highly specialized antigen-presenting cells characterized by the ability to prime T-cell responses. Mesenchymal stem cells (MSC) are adult stromal progenitor cells displaying immunomodulatory activities including inhibition of DC maturation in vitro. However, the specific impact of MSC on DC functions, upon in vivo administration, has never been elucidated. Here we show that murine MSC impair Toll-like receptor-4 induced activation of DC resulting in the inhibition of cytokines secretion, down-regulation of molecules involved in the migration to the lymph nodes, antigen presentation to CD4 + T cells, and cross-presentation to CD8 + T cells. These effects are associated with the inhibition of phosphorylation of intracellular mitogen-activated protein kinases. Intravenous administration of MSC decreased the number of CCR7 and CD49dβ1 expressing CFSE-labeled DC in the draining lymph nodes and hindered local antigen priming of DO11.10 ovalbumin-specific CD4 + T cells. Upon labeling of DC with technetium-99m hexamethylpropylene amine oxime to follow their in vivo biodistribution, we demonstrated that intravenous injection of MSC blocks, almost instantaneously, the migration of subcutaneously administered ovalbumin-pulsed DC to the draining lymph nodes. These findings indicate that MSC significantly affect DC ability to prime T cells in vivo because of their inability to home to the draining lymph nodes and further confirm MSC potentiality as therapy for immune-mediated diseases. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|