title: 1,25-Dihydroxyvitamin D3-Conditioned CD11c+ Dendritic Cells are Effective Initiators of CNS Autoimmune Disease.
abstract: Dendritic cells (DC) play a crucial role in regulating T cell activation. Due to their capacity to shape the immune response, tolerogenic DC have been used to treat autoimmune diseases. In this study, we examined whether 1,25 dihydroxyvitamin D3-conditioned bone marrow-derived DC (VitD-BMDC) were able to limit the development of autoimmune pathology in experimental autoimmune encephalomyelitis (EAE). We found that VitD-BMDC had lower expression of MHC class II and co-stimulatory molecules and were less effective at priming autoreactive T cells in vitro. Using our recently described BMDC-driven model of EAE, we demonstrated that VitD-BMDC had a significantly reduced ability to initiate EAE. We found that the impaired ability of VitD-BMDC to initiate EAE was not due to T cell tolerization. Instead, we discovered that the addition of 1,25(OH)2D3 to BMDC cultures resulted in a significant reduction in the proportion of CD11c+ cells. Purified CD11c+ VitD-BMDC were significantly less effective at priming T cells in vitro yet were similarly capable of initiating EAE as vehicle-treated CD11c+ BMDC. This study demonstrates that in vitro assays of DC function can be a poor predictor of in vivo behavior and that CD11c+ VitD-BMDC are highly effective initiators of an autopathogenic T cell response.
authors.affiliation: MRC Centre for Inflammation Research, The University of Edinburgh , Edinburgh , UK ; Centre for Multiple Sclerosis Research, The University of Edinburgh , Edinburgh , UK ; Centre for Immunity, Infection and Evolution, The University of Edinburgh , Edinburgh , UK.
authors.forename: Dario
authors.initials: D
authors.lastname: Besusso
authors.affiliation: MRC Centre for Inflammation Research, The University of Edinburgh , Edinburgh , UK ; Centre for Multiple Sclerosis Research, The University of Edinburgh , Edinburgh , UK ; Centre for Immunity, Infection and Evolution, The University of Edinburgh , Edinburgh , UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Saul
authors.affiliation: MRC Centre for Inflammation Research, The University of Edinburgh , Edinburgh , UK ; Centre for Multiple Sclerosis Research, The University of Edinburgh , Edinburgh , UK ; Centre for Immunity, Infection and Evolution, The University of Edinburgh , Edinburgh , UK.
authors.forename: Melanie D
authors.initials: MD
authors.lastname: Leech
authors.affiliation: MRC Centre for Inflammation Research, The University of Edinburgh , Edinburgh , UK ; Centre for Multiple Sclerosis Research, The University of Edinburgh , Edinburgh , UK ; Centre for Immunity, Infection and Evolution, The University of Edinburgh , Edinburgh , UK.
authors.forename: Richard A
authors.initials: RA
authors.lastname: O'Connor
authors.affiliation: Manchester Collaborative Centre for Inflammation Research, The University of Manchester , Manchester , UK.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: MacDonald
authors.affiliation: MRC Centre for Inflammation Research, The University of Edinburgh , Edinburgh , UK ; Centre for Multiple Sclerosis Research, The University of Edinburgh , Edinburgh , UK ; Centre for Immunity, Infection and Evolution, The University of Edinburgh , Edinburgh , UK.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Anderton
authors.affiliation: MRC Centre for Inflammation Research, The University of Edinburgh , Edinburgh , UK ; Centre for Multiple Sclerosis Research, The University of Edinburgh , Edinburgh , UK ; Centre for Immunity, Infection and Evolution, The University of Edinburgh , Edinburgh , UK ; The Roslin Institute, Royal (Dick) School of Veterinary Studies, The University of Edinburgh , Midlothian , UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Mellanby
keywords: T cell; dendritic cell; experimental autoimmune encephalomyelitis; multiple sclerosis; vitamin D