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1,25‐Dihydroxyvitamin D 3 alters murine dendritic cell behaviour in vitro and in vivo
Author(s) -
Ferreira Gabriela Bomfim,
van Etten Evelyne,
Verstuyf Annemieke,
Waer Mark,
Overbergh Lut,
Gysemans Conny,
Mathieu Chantal
Publication year - 2011
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.1275
Subject(s) - b cell , in vivo , in vitro , chemistry , microbiology and biotechnology , biology , immunology , antibody , biochemistry , genetics
Background Differentiation and maturation of dendritic cells yield a cell type with the ability to prime immune responses towards defence and destruction. 1,25(OH) 2 D 3 , the active form of vitamin D 3 , fosters the development of tolerogenic dendritic cells. This study aimed to evaluate the effects of 1,25(OH) 2 D 3 on murine dendritic cell behaviour in vitro and in vivo . Methods Dendritic cells were differentiated from bone marrow cells of female C57Bl/6 mice in the presence or absence of 10 −8 M 1,25(OH) 2 D 3 for 8 days (IL4 and GM‐CSF). Maturation was induced for 48 h (IFNγ, LPS and BALB/C islet homogenate antigen). Results Bone marrow‐derived dendritic cells displayed a different surface marker profile in the presence of 1,25(OH) 2 D 3 with decreased MHC II, CD86 and CD80 and increased CCR5, DEC205, F4/80 and CD40, as well as lower IL6 and IL12 expression upon LPS/IFNγ stimulation. T‐cell proliferation was significantly reduced when exposed to islet antigen‐loaded 1,25D 3 ‐DCs as compared to control dendritic cells and IL4, IL10, TNFα and TGFβ levels were increased. In vivo , transfer of islet antigen‐loaded control dendritic cells resulted in priming of the immune system and hyperacute islet allograft rejection (4/4), whereas this was prevented in 5/7 mice treated with islet antigen‐loaded 1,25D 3 ‐DCs. Conclusion We conclude that in vitro 1,25(OH) 2 D 3 exposure alters dendritic cell behaviour, converting them into a cell type that drives T cells away from destruction towards a regulatory phenotype. Copyright © 2011 John Wiley & Sons, Ltd.