Developmental Vitamin D Deficiency and the Vitamin D Receptor Control Hematopoiesis.

Vitamin D status, the vitamin D receptor (VDR), and the ability to produce active vitamin D [1,25(OH)2D, regulated by Cyp27b1] regulate fetal and adult hematopoiesis. Transgenic reporter mice that express the tdTomato RFP as an indication of Vdr expression were used to identify immune cells that express the Vdr. Vdr/tdTomato+ hematopoietic progenitors were identified as early as embryonic day (E)15.

Two lineages of immune cells that differentially express the vitamin D receptor.

Since 1983 it has been known that monocytes and activated T and B cells expressed the vitamin D receptor (VDR) and are therefore vitamin D targets. New data identified two lineages of immune cells that can be differentiated by the expression of the VDR. Monocytes, macrophages, neutrophils, and hematopoietic stem cells were mostly from VDR positive lineages.

Highlights from the 24th workshop on vitamin D in Austin, September 2022.

The 24th Workshop on Vitamin D was held September 7-9, 2022 in Austin, Texas and covered a wide diversity of research in the vitamin D field from across the globe. Here, we summarize the meeting, individual sessions, awards and presentations given.

Vitamin D and the Ability to Produce 1,25(OH)D Are Critical for Protection from Viral Infection of the Lungs.

Vitamin D supplementation is linked to improved outcomes from respiratory virus infection, and the COVID-19 pandemic renewed interest in understanding the potential role of vitamin D in protecting the lung from viral infections. Therefore, we evaluated the role of vitamin D using animal models of pandemic H1N1 influenza and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. In mice, dietary-induced vitamin D deficiency resulted in lung inflammation that was present prior to infection.

Vitamin D for COVID-19: where are we now?

Vitamin D has received much interest during the COVID-19 pandemic as a potential prophylactic or therapeutic agent — but do the available data support its use?

CCL27 is a crucial regulator of immune homeostasis of the skin and mucosal tissues.

Abundant immune cells reside in barrier tissues. Understanding the regulation of these cells can yield insights on their roles in tissue homeostasis and inflammation. Here, we report that the chemokine CCL27 is critical for establishment of resident lymphocytes and immune homeostasis in barrier tissues.

Transcriptional Profiling of the Small Intestine and the Colon Reveals Modulation of Gut Infection with According to the Vitamin A Status.

Vitamin A (VA) deficiency and diarrheal diseases are both serious public health issues worldwide. VA deficiency is associated with impaired intestinal barrier function and increased risk of mucosal infection-related mortality. The bioactive form of VA, retinoic acid, is a well-known regulator of mucosal integrity.

Novel insight into the role of the vitamin D receptor in the development and function of the immune system.

Immune cells express the vitamin D receptor (VDR) and are therefore vitamin D targets. The Vdr protein can be readily measured in the kidney using antibodies to the Vdr and western blot. It is much more difficult to measure Vdr protein in the spleen because of the low level of VDR expression in resting immune cells.

RNAseq studies reveal distinct transcriptional response to vitamin A deficiency in small intestine versus colon, uncovering novel vitamin A-regulated genes.

Vitamin A (VA) deficiency remains prevalent in resource limited areas. Using Citrobacter rodentium infection in mice as a model for diarrheal diseases, previous reports showed reduced pathogen clearance and survival due to vitamin A deficient (VAD) status. To characterize the impact of preexisting VA deficiency on gene expression patterns in the intestines, and to discover novel target genes in VA-related biological pathways, VA deficiency in mice were induced by diet.

Retinoid Signaling in Intestinal Epithelial Cells Is Essential for Early Survival From Gastrointestinal Infection.

Vitamin A deficiency (A-) increases morbidity and mortality to gastrointestinal (GI) infection. Blocking retinoid signaling (dominant negative retinoic acid receptor, dnRAR) in intestinal epithelial cells (IEC, dnRAR) had no effect on vitamin A absorption, the expression of tight junction proteins or the integrity of the barrier. Immune cells in the gut were present in normal frequencies in the dnRAR mice, with the exception of the T cell receptor (TCR)αβ+/CD8αα cells, which were significantly lower than in wildtype littermates.

Vitamin D Regulates the Microbiota to Control the Numbers of RORγt/FoxP3+ Regulatory T Cells in the Colon.

The active form of vitamin D (1,25(OH)D) suppresses experimental models of inflammatory bowel disease in part by regulating the microbiota. In this study, the role of vitamin D in the regulation of microbe induced RORγt/FoxP3+ T regulatory (reg) cells in the colon was determined. Vitamin D sufficient (D+) mice had significantly higher frequencies of FoxP3+ and RORγt/FoxP3+ T reg cells in the colon compared to vitamin D deficient (D-) mice.

Isolation and Identification of Aryl Hydrocarbon Receptor Modulators in White Button Mushrooms ().

Natural aryl hydrocarbon (AHR) ligands have been identified in food and herbal medicines, and they may exhibit beneficial activity in humans. In this study, white button (WB) feeding significantly decreased AHR target gene expression in the small intestine of both conventional and germ-free mice. High-performance liquid chromatography (HPLC) fractionation and ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) combined with an AHR-responsive cell-based luciferase gene reporter assay were used to isolate and characterize benzothiazole (BT) derivatives and 6-methylisoquinoline (6-MIQ) as AHR modulators from WB mushrooms.

Aligning the Paradoxical Role of Vitamin D in Gastrointestinal Immunity.

Inflammatory bowel disease (IBD) is a chronic disorder characterized by inflammation of the gastrointestinal tract and an immune-mediated attack against the commensal microbiota. Vitamin D is an essential vitamin that not only promotes calcium and phosphate absorption but also regulates immune function. The active form of vitamin D [1,25(OH)D] has been shown to suppress symptoms of IBD by inhibiting T cell responses.

Vitamin A and vitamin D regulate the microbial complexity, barrier function, and the mucosal immune responses to ensure intestinal homeostasis.

Diet is an important regulator of the gastrointestinal microbiota. Vitamin A and vitamin D deficiencies result in less diverse, dysbiotic microbial communities and increased susceptibility to infection or injury of the gastrointestinal tract. The vitamin A and vitamin D receptors are nuclear receptors expressed by the host, but not the microbiota.

Vitamin D Is Required for ILC3 Derived IL-22 and Protection From Infection.

is a gastrointestinal infection that requires early IL-22 from group 3 innate lymphoid cells (ILC3) for resistance. The role of vitamin D in the clearance of infection was tested in vitamin D sufficient (D+) and vitamin D deficient (D-) wildtype (WT) and Cyp27B1 (Cyp) KO mice (unable to produce the high affinity vitamin D ligand 1,25(OH)D, 1,25D). Feeding Cyp KO mice D- diets reduced vitamin D levels and prevented synthesis of 1,25D.

Retinoic Acid Mediated Clearance of in Vitamin A Deficient Mice Requires CD11b+ and T Cells.

Vitamin A deficiency affects over 250 million preschool-age children worldwide and is associated with increased childhood mortality and risk of developing enteric infections. Vitamin A deficient (A-) mice developed chronic infection. A single oral dose of retinoic acid (RA) at d7 post-infection was sufficient to induce clearance of the pathogen in A- mice.

Neuroprotective Role of the Ron Receptor Tyrosine Kinase Underlying Central Nervous System Inflammation in Health and Disease.

Neurodegeneration is a critical problem in aging populations and is characterized by severe central nervous system (CNS) inflammation. Macrophages closely regulate inflammation in the CNS and periphery by taking on different activation states. The source of inflammation in many neurodegenerative diseases has been preliminarily linked to a decrease in the CNS M2 macrophage population and a subsequent increase in M1-mediated neuroinflammation.

The Gut Microbiota Regulates Endocrine Vitamin D Metabolism through Fibroblast Growth Factor 23.

To determine the effect of the microbiota on vitamin D metabolism, serum 25-hydroxyvitamin D(25D), 24,25-dihydroxyvitamin D (24,25D), and 1,25-dihydroxyvitamin D (1,25D) were measured in germ-free (GF) mice before and after conventionalization (CN). GF mice had low levels of 25D, 24,25D, and 1,25D and were hypocalcemic. CN of the GF mice with microbiota, for 2 weeks recovered 25D, 24,25D, and 1,25D levels.

Regulation of vitamin D metabolism following disruption of the microbiota using broad spectrum antibiotics.

Vitamin D, 25hydroxyvitamin D (25D), and 24,25dihydroxyvitamin D (24,25D) were measured before and after broad spectrum antibiotic (Abx) treatment for 2 wks. Abx treatments increased 25D and 24,25D levels suggesting that the microbiota or Abx were altering vitamin D metabolism. Increased 25D, but not 24,25D, following Abx treatments were found to be dependent on toll like receptor signaling.

Vitamin A deficiency in mice alters host and gut microbial metabolism leading to altered energy homeostasis.

Vitamin A deficiency (A-) is a worldwide public health problem. To better understand how vitamin A status influences gut microbiota and host metabolism, we systematically analyzed urine, cecum, serum and liver samples from vitamin A sufficient (A+) and deficient (A-) mice using H NMR-based metabolomics, quantitative (q)PCR and 16S rRNA gene sequencing coupled with multivariate data analysis. The microbiota in the cecum of A- mice showed compositional as well as functional shifts compared to the microbiota from A+ mice.

Control of Circulating IgE by the Vitamin D Receptor In Vivo Involves B Cell Intrinsic and Extrinsic Mechanisms.

Vitamin D deficiency is associated with the development of asthma and allergy. The active form of vitamin D [1,25(OH)D] regulates B cells in vitro and mice without the vitamin D receptor (VDR knockout [KO]) have high serum IgE. Whole-body VDR KO, T cell-specific VDR (T-VDR) KO, B cell-specific VDR (B-VDR) KO, and vitamin D deficient mice were used to determine the targets of vitamin D in the regulation of IgE in vivo.

The role of UVR and vitamin D on T cells and inflammatory bowel disease.

Vitamin D deficiency is associated with the development of inflammatory bowel disease (IBD). In experimental IBD the targets of vitamin D that result in protection from IBD include gut epithelial cells, innate immune cells, T cells, and the microbiota. Ultraviolet radiation (UVR) induces production of vitamin D in the skin and suppresses T cell responses in the host.

Vitamin D and Lung Infection.

Available data suggest that vitamin D plays a role in controlling inflammation in the lungs. However, to date vitamin D-induced production of cathelicidin has not been shown to have an effect on the burden of either viruses or bacteria. Future work should continue to determine the effects of vitamin D-regulated mechanisms in the lung and the possible role of cathelicidin against different pulmonary pathogens in vivo.