Dendritic cell modulation by 1α,25 dihydroxyvitamin D3and its analogs: A vitamin D receptor-dependent pathway that promotes a persistent state of immaturityin vitroandin vivo

• DOI: 10.1073/pnas.121172198
• Publication Date: 2002-07-26T14:44:19Z
• Authors: Matthew D. Griffin; Ward Lutz; Vy A. Phan; Lori A. Bachman; David J. McKean; Rajiv Kumar
• Keywords: Male; Membrane Glycoproteins; Dendritic Cells; Skin Transplantation; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; 0302 clinical medicine; Calcitriol; Antigens, CD; Transforming Growth Factor beta; B7-1 Antigen; Animals; Receptors, Calcitriol; Female; B7-2 Antigen

Dendritic cells (DCs) play a central role in regulating immune activation and responses to self. DC maturation is the outcome of antigen presentation T cells. Maturation DCs inhibited by physiological levels 1α,25 dihydroxyvitamin D 3 [1α,25(OH) 2 ] related analog, 1α,25(OH) -16-ene-23-yne-26,27-hexafluoro-19-nor-vitamin (D analog). Conditioning bone marrow cultures with 10 −10 M analog resulted accumulation immature reduced IL-12 secretion without induction transforming growth factor β1. These retained an phenotype after withdrawal exhibited blunted maturing stimuli (CD40 ligation, macrophage products, or lipopolysaccharide). Resistance depended on presence receptor (VDR). In vivo model DC-mediated antigen-specific sensitization, analog-conditioned failed sensitize and, instead, promoted prolonged survival subsequent skin grafts expressing same antigen. To investigate physiologic significance /VDR-mediated modulation maturity we analyzed populations from mice lacking VDR. Compared wild-type animals, VDR-deficient had hypertrophy subcutaneous lymph nodes increase mature but not spleen. We conclude that /VDR mediates physiologically relevant inhibition resistant maturational modulates .