Mesenchymal stem cells impair in vivo T-cell priming by dendritic cells

Sabrina Chiesa, Silvia Morbelli, Sara Morando, Michela Massollo, Cecilia Marini, Arinna Bertoni, Francesco Frassoni, Soraya Tabera Bartolomé, Gianmario Sambuceti, Elisabetta Traggiai, Antonio Uccelli

Research output: Contribution to journalArticlepeer-review

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 thatMSC significantly affect DC ability to prime T cells in vivo because of their inability to home to the draining lymph nodes and further confirmMSC potentiality as therapy for immune-mediated diseases.

Original languageEnglish
Pages (from-to)17384-17389
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number42
DOIs
Publication statusPublished - Oct 18 2011

Keywords

  • Immunomodulation
  • Tolerance

ASJC Scopus subject areas

  • General

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