In Vitro and In Vivo Analysis of the Immune System of Vitamin D Receptor Knockout Mice

• DOI: 10.1359/jbmr.2001.16.11.2057
• Publication Date: 2006-04-27T03:34:56Z
• Authors: Chantal Mathieu; Evelyne Van Etten; Conny Gysemans; Brigitte Decallonne; Shigeaki Kato; Jos Laureys; JOS Depovere; Dirk Valckx; Annemieke Verstuyf; Roger Bouillon
• Keywords: Knockout mouse

Abstract Immune cells carry receptors for 1,25-dihydroxyvitamin D3 [1,25(OH)2D3; vitamin D receptor (VDR)] and individuals with severe deficiency have immune abnormalities. The aim of this study was to investigate the role in system by studying VDR-knockout (VDR-KO) mice. VDR-KO mice had same metabolic phenotype as rachitic animals hypocalcemia. Leukocytosis, lymphocyte subset composition different organs, splenocyte proliferation several stimuli were normal, except a lower response anti-CD3 stimulation (simulation index [SI] 13 ± 4 vs. 24 9 wild-type mice; p < 0.01). Macrophage chemotaxis impaired (41 19% 60 18% 0.01) but phagocytosis killing normal. In vivo rejection allogeneic (31 12 days 45 26 survival mice, NS) or xenogeneic (10 2 16 islet grafts comparable Surprisingly, protected from low-dose streptozotocin-induced diabetes mellitus (LDSDM; 5% 65% 0.001). Correcting hypocalcemia use lactose-rich polyunsaturated fat-rich diets fully restored abnormalities vitro sensitivity vivo. On other hand, treatment 1,25(OH)2D3 against did not protect normocalcemic We conclude that defects observed are an indirect consequence VDR disruption because they can be calcium homeostasis normalization. This proves although is pharmacologic probably physiological immunomodulator, its function redundant. Moreover, we confirm essential system.