Vitamin D And The Vitamin D Receptor Regulate Development And Function Of The Immune System

Active vitamin D ligand, 1alpha,25-dihydroxyvitaminD (1,25D), binds to the vitamin D receptor (VDR), and the ligand-activated complex further regulates transcription of various genes within the target cell. Thus, cells that express the VDR are vitamin D targets. VDR is expressed in immune cells including dendritic cells, macrophages, neutrophils, T cells and B cells. Danger signals such as lipopolysaccharide (LPS), interferon (IFN)-gamma and activation of T and B cells have been shown to regulate the expression of the VDR, implicating its role in modulating immunity. VDR polymorphisms and vitamin D deficiency in humans have been associated with the increased risk of autoimmune diseases such as inflammatory bowel diseases (IBD) and higher susceptibility to both bacterial and viral infections. Identification of vitamin D targets in the immune system and modifying the host immune response through regulation of vitamin D levels is of great clinical significance. We utilized a novel transgenic reporter mouse to lineage trace immune cells that express the VDR. Our data show that both innate (macrophages, monocytes, neutrophils) and adaptive (B and T cells) splenic immune cells expressed tdTomato. Innate lymphoid cells (ILC) 1 and 3 in lungs, small intestine, and colon expressed tdTomato while ILC2 cells did not. Bone marrow (BM) hematopoietic progenitors and thymic T cell progenitors were predominately positive for tdTomato. Peripheral immune cells and their developmental progenitors are tdTomato+ and therefore targets of vitamin D. We sorted tdTomato+ and tdTomato- T cells and studied their response in vitro. Activated tdTomato- T cells did not become tdTomato+, the tdTomato- T cells proliferated faster and produced more IFN-gamma as compared to tdTomato+ T cells. Thus, tdTomato+ and tdTomato- T cells are functionally distinct. Due to the high expression of tdTomato noted in BM progenitors, we further wanted to investigate whether VDR+ and VDR progenitors can be detected earlier in development. tdTomato expression was found in the fetal liver and fetal thymus at embryonic (E) day E15.5. Maternal vitamin D deficiency affected the frequency of fetal hematopoietic progenitors and tdTomato expression, suggesting that the availability of maternal 25-hydroxyvitaminD is needed for fetal liver hematopoiesis and thymopoiesis. Vitamin D deficiency also affected the frequency of tdTomato+ T cells in the spleen and ILCs in the lungs of mice post-birth, highlighting that VDR+ lineage continues to develop after birth. VDR knockout (KO) embryos showed fewer hematopoietic progenitors, while VDR KO adult mice had more hematopoietic progenitors. The effects of vitamin D deficiency (D-) and oral supplementation with vitamin D3 (cholecalciferol) on the outcomes of H1N1 influenza and SARS-CoV-2 infection in animal models was determined. D- mice experienced higher respiratory distress post H1N1 infection. Mice with deletion of Cyp27B1 gene and inability to produce 1,25D had decreased survival post H1N1 infection. SARS-CoV-2 infection induced the expression of vitamin D related genes in the lungs of infected mice. High dose vitamin D3 supplementation reduced lung inflammation in mice infected with SARS-CoV-2. Thus, vitamin D and vitamin D receptor play important roles in development and function of the immune system.

Principles of Bone Biology provides the most comprehensive, authoritative reference on the study of bone biology and related diseases. It is the essential resource for anyone involved in the study of bone biology. Bone research in recent years has generated enormous attention, mainly because of the broad public health implications of osteoporosis and related bone disorders. Provides a "one-stop" shop. There is no need to search through many research journals or books to glean the information one wants...it is all in one source written by the experts in the field The essential resource for anyone involved in the study of bones and bone diseases Takes the reader from the basic elements of fundamental research to the most sophisticated concepts in therapeutics Readers can easily search and locate information quickly as it will be online with this new edition

This book is a printed edition of the Special Issue "Vitamin D and Human Health" that was published in Nutrients

This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.

The second edition of this encyclopedia presents over 400 biologically important signaling molecules and the content is built on the core concepts of their functions along with early findings written by some of the world’s foremost experts. The molecules are described by recognized leaders in each molecule. The interactions of these single molecules in signal transduction networks will also be explored. This encyclopedia marks a new era in overview of current cellular signaling molecules for the specialist and the interested non-specialist alike. Currently, there are more than 30,000 genes in human genome. However, not all the proteins encoded by these genes work equally in order to maintain homeostasis. Understanding the important signaling molecules as completely as possible will significantly improve our research-based teaching and scientific capabilities.

This book examines the sometimes controversial role of vitamin D in various health problems. Divided into four sections, chapters cover such topics as vitamin D deficiency in women, newborns, and the elderly, as well as the role of vitamin D in COVID-19, autism spectrum disorder, diabetes, dental diseases, and central nervous system pathological processes.

Leukocyte culture conferences have a long pedigree. This volume records some of the scientific highlights of the 16th such annual con ference, and is a witness to the continuing evolution and popularity of leukocyte culture and of immunology. There is strong evidence of the widening horizons of immunology, both technically, with the obviously major impact of molecular biology into our understanding of cellular processes, and also conceptually. Traditionally, the 'proceedings' of these conferences have been published. But have the books produced really recorded the major part of the conference, the informal, friendly, but intense and some times heated exchanges that take place between workers in tackling very similar problems and systems and which are at the heart of every successful conference? Unfortunately this essence cannot be incorpo rated by soliciting manuscripts. For this reason, we have changed the format of publication, retaining published versions of the symposium papers, but requesting the workshop chairmen to produce a summary of the major new observations and areas of controversy highlighted in their sessions, as a vehicle for defining current areas of interest and debate. Not an easy task, as the workshop topics were culled from the abstracts submitted by the participants, rather than being on predefined topics. The unseasonal warmth in Cambridge was reflected in the atmos phere of the conference, the organization of which benefited from the administrative skills of Jean Bacon, Philippa Wells, Mr. Peter Irving, and Mrs.

Vitamin D: Volume One: Biochemistry, Physiology and Diagnostics, Fourth Edition, presents the latest information from international experts in endocrinology, bone biology and human physiology, taking readers through the basic research of vitamin D. This impressive reference presents a comprehensive review of the multifaceted vitamin D. Researchers from all areas will gain insight into how clinical observations and practices can feed back into the research cycle, thus allowing them to develop more targeted genomic and proteomic insights on the mechanisms of disease. Offers a comprehensive reference, ranging from basic bone biology, to biochemistry, to the clinical diagnostic and management implications of vitamin D Saves researchers and clinicians time in quickly accessing the very latest details on the diverse scientific and clinical aspects of Vitamin D, as opposed to searching through thousands of journal articles Targets chemistry, metabolism and circulation, mechanisms of action, mineral and bone homeostasis, human physiology, diagnosis and management, nutrition, sunlight, genetics and vitamin D deficiency Volume II of this collection presents a clinical focus on disorders, analogs, cancer; immunity, inflammation and disease and therapeutic applications

This issue features internationally renowned experts who have provided their expertise on a variety of topics related to the importance of vitamin D. It was not until feed back loops were identified between Vitamin D production and parathyroid hormone, phosphate that it earned its place as a true endocrine hormone. Current social and economic conditions have brought it back into the limelight with outbreaks of rickets and osteomalacia even in developed countries. However its complex regulation, together with the identification and characterization of the vitamin D receptor and its role in influencing multiple genetic pathways and function has heralded a new era highlighting its importance in health and disease. This includes its role in auto immune diseases such as multiple sclerosis, diabetes mellitus, cancer especially breast and prostate, skin, neurological and cognitive disorders and infectious diseases such as tuberculosis. We now know that adequate levels of vitamin D it is important in preventing falls and fracture. The need for supplementation and the amount recommended has also changed considerably from what we previously considered sufficient. The ongoing development of selective active analogs of vitamin D targeted to specific organs and function leads to the exciting possibility of improving outcomes of diseases associated with vitamin D regulation.