title: Mesenchymal stem cells impair in vivo T-cell priming by dendritic cells.
abstract: 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.
authors.affiliation: Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, 16132 Genoa, Italy. sabrina.chiesa@ospedale-gaslini.ge.it
authors.forename: Sabrina
authors.initials: S
authors.lastname: Chiesa
authors.forename: Silvia
authors.initials: S
authors.lastname: Morbelli
authors.forename: Sara
authors.initials: S
authors.lastname: Morando
authors.forename: Michela
authors.initials: M
authors.lastname: Massollo
authors.forename: Cecilia
authors.initials: C
authors.lastname: Marini
authors.forename: Arinna
authors.initials: A
authors.lastname: Bertoni
authors.forename: Francesco
authors.initials: F
authors.lastname: Frassoni
authors.forename: Soraya Tabera
authors.initials: ST
authors.lastname: Bartolomé
authors.forename: Gianmario
authors.initials: G
authors.lastname: Sambuceti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Traggiai
authors.forename: Antonio
authors.initials: A
authors.lastname: Uccelli
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000502:physiology / Q000637:transplantation; D015870:Gene Expression; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology
chemical_list: D016207:Cytokines; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4