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

Mathieu, Chantal; Etten, Evelyne van; Gysemans, Conny; Decallonne, Brigitte; Kato, Shigeaki; Laureys, Jozef; Depovere, Jos; Valckx, Dirk; Verstuyf, Annemieke; Bouillon, Roger

doi:10.1359/jbmr.2001.16.11.2057

Cited by 151 publications

(110 citation statements)

References 34 publications

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“…Analysis of the immune system of the vitamin Ddeficient mice at 100 days of age, time when animals were switched to normal food, showed major abnormalities in macrophage behaviour. The differences were, however, not situated in impaired phagocytosis or chemotaxis, previously observed in severe rickets [7,25,26,27]. The near normal phagocytic and chemotactic capacity confirms again the relevance of our model, where we did not create severely rachitic mice, but only induced a vitamin deficiency frequently observed in children.…”

Section: Discussionsupporting

confidence: 76%

“…For analysis of macrophage function, whole blood and peritoneal macrophages were used in parallel tests. Peritoneal macrophages were harvested as described previously [7]. Briefly, mice were anaesthetised with diethylether and injected intraperitoneally with 10 ml of RPMI 1640 medium.…”

Section: Animalsmentioning

confidence: 99%

“…Cells were counted and suspended to a concentration of 1×10 6 cells/ml in complete culture medium. For macrophage chemotactic evaluation, the ability of binding casein was measured as described previously [7]. Chemotactic capacity was expressed as percent of fluoresceinpositive cells.…”

Section: Animalsmentioning

confidence: 99%

“…Chemotaxis was evaluated in a similar manner as was done for peritoneal macrophages. In addition, formylNle-Leu-Phe-Nle-Tyr-Lys fluorescein derivative (fnlpntl) was also used to evaluate chemotaxis capacity of neutrophils, as described before [7]. Phagocytosis capacity was measured by flow cytometry using PHAGOTEST (Orpegen Pharma).…”

Section: Animalsmentioning

confidence: 99%

“…The discovery of the presence of receptors for the active form of vitamin D, 1α,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) in several cells of the immune system, such as macrophages, dendritic cells, B lymphocytes and activated T lymphocytes has strengthened the idea that vitamin D might function as a physiological immune modulator [7]. In different animal models of autoimmune diseases administration of high doses of 1,25(OH) 2 D 3 is able to prevent disease [8,9,10,11,12] and in recent years both T lymphocytes and antigen presenting cells, especially dendritic cells, have been identified as main targets for 1,25(OH) 2 D 3 in the immune system [13].…”

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confidence: 99%

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Vitamin D deficiency in early life accelerates Type 1 diabetes in non-obese diabetic mice

et al. 2004

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Aims/hypothesis. 1,25-dihydroxyvitamin D 3 , the active form of vitamin D, prevents Type 1 diabetes in non-obese diabetic (NOD) mice. Epidemiological data show a threefold increase in human Type 1 diabetes when vitamin D deficiency was present in the first months of life. To evaluate whether a similar dietary deficiency affects diabetes incidence in NOD mice, we generated NOD mice with vitamin D deficiency in early life. Methods. Breeding pairs of NOD mice, as well as their offspring (test mice), were kept in surroundings devoid of ultraviolet light and were fed a vitamin Ddepleted diet for 100 days. Mice were followed for 250 days. Results. At 250 days, 35% (12/35) male and 66% (22/33) female vitamin D-deficient mice were diabetic compared to 15% (6/40, p=0.05) and 45% (13/29, p<0.01) of the control mice. At 100 days no difference in insulitis was seen, but more vitamin D-deficient mice were glucose intolerant. Higher IL1 expression was detected in islets of vitamin D-deficient mice and their peritoneal macrophages had an aberrant cytokine profile (low IL1 and IL6, high IL15). Thymus and lymph nodes of vitamin D-deficient mice contained less CD4 + CD62L + cells. Conclusion/interpretation. Vitamin D status increases the expression of Type 1 diabetes in NOD mice. Our data in NOD mice, as well as human epidemiological data, point to the importance of preventing vitamin D deficiency in early childhood. Controlling this dietary factor could be an easy and safe way to reduce the incidence of Type 1 diabetes in subjects who are genetically at risk. [Diabetologia (2004)

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Section: Discussionsupporting

confidence: 76%

Section: Animalsmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

mentioning

confidence: 99%

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Vitamin D deficiency in early life accelerates Type 1 diabetes in non-obese diabetic mice

et al. 2004

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The pleiotropic actions of vitamin D

2003

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General knowledge of the role of vitamin D3 in human physiology has been shaped by its discovery as a preventive agent of nutritional rickets, a defect in bone development due to inadequate uptake of dietary calcium. Studies on the function of the hormonal form of vitamin D3, 1alpha,25-dihydroxyvitamin D3, have been greatly accelerated by the molecular cloning and structural analysis of the vitamin D3 receptor, which is a ligand-activated regulator of gene transcription. Molecular genetic techniques including genomics have helped reveal that 1alpha,25-dihydroxyvitamin D3 can control more than calcium homeostasis. It has widespread effects on cellular differentiation and proliferation, and can modulate immune responsiveness, and central nervous system function. Moreover, accumulating epidemiological and molecular evidence suggests that 1alpha,25-dihydroxyvitamin D3 acts as a chemopreventive agent against several malignancies including cancers of the prostate and colon. Here, we survey the most-recent findings and discuss their implications for the potential therapeutic uses of vitamin D analogues.

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Vitamin D and Immune Regulation: Antibacterial, Antiviral, Anti‐Inflammatory

et al. 2020

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Regulation of immune function continues to be one of the most well-recognized extraskeletal actions of vitamin D. This stemmed initially from the discovery that antigen presenting cells such as macrophages could actively metabolize precursor 25-hydroxyvitamin D (25D) to active 1,25-dihydroxyvitamin D (1,25D). Parallel observation that activated cells from the immune system expressed the intracellular vitamin D receptor (VDR) for 1,25D suggested a potential role for vitamin D as a localized endogenous modulator of immune function. Subsequent studies have expanded our understanding of how vitamin D exerts effects on both the innate and adaptive arms of the immune system. At an innate level, intracrine synthesis of 1,25D by macrophages and dendritic cells stimulates expression of antimicrobial proteins such as cathelicidin, as well as lowering intracellular iron concentrations via suppression of hepcidin. By potently enhancing autophagy, 1,25D may also play an important role in combatting intracellular pathogens such as M. tuberculosis and viral infections. Local synthesis of 1,25D by macrophages and dendritic cells also appears to play a pivotal role in mediating T-cell responses to vitamin D, leading to suppression of inflammatory T helper (Th)1 and Th17 cells, and concomitant induction of immunotolerogenic Tregulatory responses. The aim of this review is to provide an update on our current understanding of these prominent immune actions of vitamin D, as well as highlighting new, less well-recognized immune effects of vitamin D. The review also aims to place this mechanistic basis for the link between vitamin D and immunity with studies in vivo that have explored a role for vitamin D supplementation as a strategy for improved immune health. This has gained prominence in recent months with the global coronavirus disease 2019 health crisis and highlights important new objectives for future studies of vitamin D and immune function.

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

Abstract: ABSTRACT

Cited by 151 publications

References 34 publications

Vitamin D deficiency in early life accelerates Type 1 diabetes in non-obese diabetic mice

Vitamin D deficiency in early life accelerates Type 1 diabetes in non-obese diabetic mice

The pleiotropic actions of vitamin D

Vitamin D and Immune Regulation: Antibacterial, Antiviral, Anti‐Inflammatory

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