TY - JOUR
T1 - Mesenchymal stem cells impair in vivo T-cell priming by dendritic cells
AU - Chiesa, Sabrina
AU - Morbelli, Silvia
AU - Morando, Sara
AU - Massollo, Michela
AU - Marini, Cecilia
AU - Bertoni, Arinna
AU - Frassoni, Francesco
AU - Bartolomé, Soraya Tabera
AU - Sambuceti, Gianmario
AU - Traggiai, Elisabetta
AU - Uccelli, Antonio
PY - 2011/10/18
Y1 - 2011/10/18
N2 - 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.
AB - 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.
KW - Immunomodulation
KW - Tolerance
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U2 - 10.1073/pnas.1103650108
DO - 10.1073/pnas.1103650108
M3 - Article
C2 - 21960443
AN - SCOPUS:80054809361
VL - 108
SP - 17384
EP - 17389
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 42
ER -