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
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)
- author
- 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. (More)
- 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
; Korf, Hannelie
and Mathieu, Chantal
(Less)
- publishing date
- 2014-05-01
- 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
- 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
- 2024-04-01 21:57:26
@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}},
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}},
language = {{eng}},
month = {{05}},
number = {{9}},
pages = {{4210--4220}},
publisher = {{American Association of Immunologists}},
series = {{Journal of immunology}},
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}},
}