Advanced

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

Ferreira, Gabriela B LU ; Gysemans, Conny A ; Demengeot, Jocelyne ; da Cunha, João Paulo M C M LU ; Vanherwegen, An-Sofie ; Overbergh, Lut ; Van Belle, Tom L ; Pauwels, Femke ; Verstuyf, Annemieke and Korf, Hannelie , et al. (2014) In Journal of immunology (Baltimore, Md. : 1950) 192(9). p.4210-4220
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; and (Less)
publishing date
type
Contribution to journal
publication status
published
subject
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
in
Journal of immunology (Baltimore, Md. : 1950)
volume
192
issue
9
pages
11 pages
publisher
American Association of Immunologists
external identifiers
  • pmid:24663679
  • scopus:84899562215
ISSN
1550-6606
DOI
10.4049/jimmunol.1302350
language
English
LU publication?
no
id
9f6f7f7d-b415-451c-b487-39b386b95fde
date added to LUP
2019-02-14 09:39:00
date last changed
2020-09-30 05:59:32
@article{9f6f7f7d-b415-451c-b487-39b386b95fde,
  abstract     = {<p>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. </p>},
  author       = {Ferreira, Gabriela B and Gysemans, Conny A and Demengeot, Jocelyne and da Cunha, João Paulo M C M and Vanherwegen, An-Sofie and Overbergh, Lut and Van Belle, Tom L and Pauwels, Femke and Verstuyf, Annemieke and Korf, Hannelie and Mathieu, Chantal},
  issn         = {1550-6606},
  language     = {eng},
  month        = {05},
  number       = {9},
  pages        = {4210--4220},
  publisher    = {American Association of Immunologists},
  series       = {Journal of immunology (Baltimore, Md. : 1950)},
  title        = {1,25-Dihydroxyvitamin D3 promotes tolerogenic dendritic cells with functional migratory properties in NOD mice},
  url          = {http://dx.doi.org/10.4049/jimmunol.1302350},
  doi          = {10.4049/jimmunol.1302350},
  volume       = {192},
  year         = {2014},
}