AIMS/HYPOTHESIS: Mesenchymal stem cells (MSCs) can exert an immunosuppressive effect on any component of the immune system, including dendritic cells (DCs), by direct contact, the release of soluble markers and extracellular vesicles (EVs). We evaluated whether MSCs and MSC-derived EVs have an immunomodulatory effect on monocyte-derived DCs in type 1 @entity6 . METHODS: Bone marrow derived MSCs were characterised and EVs were obtained by ultracentrifugation. DCs were differentiated from @entity5750 (+) cells, obtained from nine type 1 @entity6 @entity1 at disease onset, pulsed with antigen @entity1840 and cultured with MSCs or EVs. Levels of DC maturation and activation markers were evaluated by flow cytometry. @entity1840 -pulsed DCs and autologous @entity5750 (-) cell were co-cultured and @entity379 enzyme-linked immunosorbent spot responses were assayed. Secreted cytokine levels were measured and Th17 and regulatory T cells were analysed. RESULTS: MSC- and EV-conditioned DCs acquired an immature phenotype with reduced levels of activation markers and increased @entity688 and @entity650 production. Conditioned DC plus T cell co-cultures showed significantly decreased @entity379 spots and secretion levels. Moreover, higher levels of TGF-b, @entity688 and @entity650 were detected compared with unconditioned DC plus T cell co-cultures. Conditioned DCs decreased Th17 cell numbers and @entity4155 levels, and increased @entity403 (+) regulatory T cell numbers. EVs were internalised by DCs and EV-conditioned DCs exhibited a similar effect. CONCLUSIONS/INTERPRETATION: In type 1 @entity6 , MSCs induce immature @entity688 -secreting DCs in vitro, thus potentially intercepting the priming and amplification of autoreactive T cells in tissue @entity32 . These DCs can contribute to the inhibition of inflammatory T cell responses to islet antigens and the promotion of the anti-inflammatory, regulatory responses exerted by MSCs.

@entity1 mesenchymal stem cells and derived extracellular vesicles induce regulatory dendritic cells in type 1 @entity6 XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity650 :: ('3569', 'Gene') :: ['IL-6'] @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity6 :: ('MESH:D003920', 'Disease') :: ['diabetic', 'diabetes'] @entity1840 :: ('2572', 'Gene') :: ['GAD65'] @entity5750 :: ('929', 'Gene') :: ['CD14'] @entity4155 :: ('3605', 'Gene') :: ['IL-17'] @entity379 :: ('3458', 'Gene') :: ['IFN-y'] @entity403 :: ('50943', 'Gene') :: ['FOXP3'] @entity688 :: ('3586', 'Gene') :: ['IL-10']
@entity1 :: (9606,Species) :: ['patients']
