1,25-Dihydroxyvitamin D3 promotes tolerogenic dendritic cells with functional migratory properties in NOD mice

The biologically active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], is able to promote the generation of tolerogenic mature dendritic cells (mDCs) with an impaired ability to activate autoreactive T cells. These cells could represent a reliable tool for the promotion or restoration of Ag-specific tolerance through vaccination strategies, for example in type 1 diabetes patients. However, successful transfer of 1,25(OH)2D3-treated mDCs (1,25D3-mDCs) depends on the capacity of 1,25(OH)2D3 to imprint a similar tolerogenic profile in cells derived from diabetes-prone donors as from diabetes-resistant donors. In this study, we examined the impact of 1,25(OH)2D3 on the function and phenotype of mDCs originating from healthy (C57BL/6) and diabetes-prone (NOD) mice. We show that 1,25(OH)2D3 is able to imprint a phenotypic tolerogenic profile on DCs derived from both mouse strains. Both NOD- and C57BL/6-derived 1,25D3-mDCs decreased the proliferation and activation of autoreactive T cells in vitro, despite strain differences in the regulation of cytokine/chemokine expression. In addition, 1,25D3-mDCs from diabetes-prone mice expanded CD25(+)Foxp3(+) regulatory T cells and induced intracellular IL-10 production by T cells in vitro. Furthermore, 1,25D3-mDCs exhibited an intact functional migratory capacity in vivo that favors homing to the liver and pancreas of adult NOD mice. More importantly, when cotransferred with activated CD4(+) T cells into NOD.SCID recipients, 1,25D3-mDCs potently dampened the proliferation of autoreactive donor T cells in the pancreatic draining lymph nodes. Altogether, these results argue for the potential of 1,25D3-mDCs to restore Ag-specific immune tolerance and arrest autoimmune disease progression in vivo.

Description

This deposit is composed by a publication in which the IGC's authors have had the role of collaboration (it's a collaboration publication). This type of deposit in ARCA is in restrictedAccess (it can't be in open access to the public), and can only be accessed by two ways: either by requesting a legal copy from the author (the email contact present in this deposit) or by visiting the following link: http://www.jimmunol.org/content/192/9/4210.long#ack-1
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Keywords

Animals Chemotaxis, Leukocyte Dendritic Cells Flow Cytometry Fluorescent Antibody Technique Immune Tolerance Lymphocyte Activation Mice Mice, Inbred C57BL Mice, Inbred NOD Mice, Transgenic Phenotype Real-Time Polymerase Chain Reaction Vitamin D

URI

http://hdl.handle.net/10400.7/848

Citation

1,25-Dihydroxyvitamin D3 Promotes Tolerogenic Dendritic Cells with Functional Migratory Properties in NOD Mice Gabriela B. Ferreira, Conny A. Gysemans, Jocelyne Demengeot, João Paulo M. C. M. da Cunha, An-Sofie Vanherwegen, Lut Overbergh, Tom L. Van Belle, Femke Pauwels, Annemieke Verstuyf, Hannelie Korf, Chantal Mathieu The Journal of Immunology May 1, 2014, 192 (9) 4210-4220; DOI: 10.4049/jimmunol.1302350