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

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
  • 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
External organisations
  • Catholic University of Leuven
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area

Keywords

  • Animals, Chemotaxis, Leukocyte/drug effects, Dendritic Cells/cytology, Flow Cytometry, Fluorescent Antibody Technique, Immune Tolerance/drug effects, Lymphocyte Activation/drug effects, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, Transgenic, Phenotype, Real-Time Polymerase Chain Reaction, Vitamin D/analogs & derivatives
Original languageEnglish
Pages (from-to)4210-4220
Number of pages11
JournalJournal of immunology (Baltimore, Md. : 1950)
Volume192
Issue number9
Publication statusPublished - 2014 May 1
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes