1α,25-Dihydroxyvitamin D3 Inhibits Differentiation, Maturation, Activation, and Survival of Dendritic Cells Leading to Impaired Alloreactive T Cell Activation
2000/03/01 by Giuseppe Penna, Luciano Adorini · 1,263 citations
Chemistry · Immunology and Microbiology · #Biochemistry #Biology #CD40 #CD80 #CD86 #Cell biology #Chemistry #Cytotoxic T cell #Dendritic cell #Endocrinology #Immune Cell Function and Interaction #Immune system #Immunology #Immunotherapy and Immune Responses #In vitro #MHC class II #Secretion #T cell #T-cell and B-cell Immunology
paper · doi:10.4049/jimmunol.164.5.2405
published in The Journal of Immunology 164(5), 2405-2411 (American Association of Immunologists)
openalex publication_date 2000/03/01 · openalex created_date 2016/06/24 · openalex updated_date 2026/07/28
Abstract
1 Alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active form of vitamin D3, is a potent immunomodulatory agent. Here we show that dendritic cells (DCs) are major targets of 1,25(OH)2D3-induced immunosuppressive activity. 1,25(OH)2D3 prevents the differentiation in immature DCs of human monocytes cultured with GM-CSF and IL-4. Addition of 1,25(OH)2D3 during LPS-induced maturation maintains the immature DC phenotype characterized by high mannose receptor and low CD83 expression and markedly inhibits up-regulation of the costimulatory molecules CD40, CD80, and CD86 and of class II MHC molecules. This is associated with a reduced capacity of DCs to activate alloreactive T cells, as determined by decreased proliferation and IFN-gamma secretion in mixed leukocyte cultures. 1, 25(OH)2D3 also affects maturing DCs, leading to inhibition of IL-12p75 and enhanced IL-10 secretion upon activation by CD40 ligation. In addition, 1,25(OH)2D3 promotes the spontaneous apoptosis of mature DCs. The modulation of phenotype and function of DCs matured in the presence of 1,25(OH)2D3 induces cocultured alloreactive CD4+ cells to secrete less IFN-gamma upon restimulation, up-regulate CD152, and down-regulate CD154 molecules. The inhibition of DC differentiation and maturation as well as modulation of their activation and survival leading to T cell hyporesponsiveness may explain the immunosuppressive activity of 1, 25(OH)2D3.
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