TY - JOUR

T1 - 1,25-Dihydroxyvitamin D3 promotes tolerogenic dendritic cells with functional migratory properties in NOD Mice

AU - Ferreira, Gabriela B.

AU - Gysemans, Conny A.

AU - Demengeot, Jocelyne

AU - Da Cunha, Joaõ Paulo M.C.M.

AU - Vanherwegen, An Sofie

AU - Overbergh, Lut

AU - Van Belle, Tom L.

AU - Pauwels, Femke

AU - Verstuyf, Annemieke

AU - Korf, Hannelie

AU - Mathieu, Chantal

PY - 2014

Y1 - 2014

N2 - The biologically active form of vitamin D, 1,25-dihydroxyvitamin D 3 [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 (1,25D 3-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, 1,25D 3-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. The Journal of Immunology, 2014, 192: 4210-4220.

AB - The biologically active form of vitamin D, 1,25-dihydroxyvitamin D 3 [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 (1,25D 3-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, 1,25D 3-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. The Journal of Immunology, 2014, 192: 4210-4220.

UR - http://www.scopus.com/inward/record.url?scp=84899562215&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1302350

DO - 10.4049/jimmunol.1302350

M3 - Journal article

C2 - 24663679

AN - SCOPUS:84899562215

VL - 192

SP - 4210

EP - 4220

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 9

ER -