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The immunological functions of the vitamin D endocrine system.
Cell Mol Biol (Noisy-le-grand). 2003 Mar; 49(2):277-300.CM

Abstract

The discoveries that activated macrophages produce 1alpha25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3), and that immune system cells express the vitamin D receptor (VDR), suggested that the vitamin D endocrine system influences immune system function. In this review, we compare and contrast how 1alpha,25-(OH)2D3 synthesis and degradation is regulated in kidney cells and activated macrophages, summarize data on hormone receptor function and expression in lymphocytes and myeloid lineage cells, and discuss how locally-produced 1alpha,25-(OH)2D3 may activate a negative feed-back loop at sites of inflammation. Studies of immunity in humans and animals lacking VDR function, or lacking vitamin D, are viewed to gain insight into the immunological functions of the vitamin D endocrine system. The strong associations between poor vitamin D nutrition, particular VDR alleles, and susceptibility to chronic mycobacterial infections, together with evidence that 1alpha,25-(OH)2D3 served as a vaccine adjuvant enhancing antibody-mediated immunity, suggest a model wherein high levels of 1alpha,25-(OH)2D3-liganded VDR transcriptional activity may promote the CD4+ T helper 2 (Th2) cell-mediated and mucosal antibody responses to cutaneous antigens in vivo. We also review a diverse and rapidly growing body of epidemiological, climatological, genetic, nutritional and biological evidence indicating that the vitamin D endocrine system functions in the establishment and/or maintenance of immunological self tolerance. Studies done in animal models of multiple sclerosis (MS), insulin-dependent diabetes mellitus (IDDM), inflammatory bowel disease (IBD), and transplantation support a model wherein the 1alpha,25-(OH)2D3 may augment the function of suppressor T cells that maintain self tolerance to organ-specific self antigens. The recent progress in infectious disease, autoimmunity and transplantation has stimulated a gratifying renaissance of interest in the vitamin D endocrine system and its role in immunological health.

Authors+Show Affiliations

Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, Wisconsin 53706, USA. hayes@biochem.wisc.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

12887108

Citation

Hayes, C E., et al. "The Immunological Functions of the Vitamin D Endocrine System." Cellular and Molecular Biology (Noisy-le-Grand, France), vol. 49, no. 2, 2003, pp. 277-300.
Hayes CE, Nashold FE, Spach KM, et al. The immunological functions of the vitamin D endocrine system. Cell Mol Biol (Noisy-le-grand). 2003;49(2):277-300.
Hayes, C. E., Nashold, F. E., Spach, K. M., & Pedersen, L. B. (2003). The immunological functions of the vitamin D endocrine system. Cellular and Molecular Biology (Noisy-le-Grand, France), 49(2), 277-300.
Hayes CE, et al. The Immunological Functions of the Vitamin D Endocrine System. Cell Mol Biol (Noisy-le-grand). 2003;49(2):277-300. PubMed PMID: 12887108.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The immunological functions of the vitamin D endocrine system. AU - Hayes,C E, AU - Nashold,F E, AU - Spach,K M, AU - Pedersen,L B, PY - 2003/7/31/pubmed PY - 2004/3/11/medline PY - 2003/7/31/entrez SP - 277 EP - 300 JF - Cellular and molecular biology (Noisy-le-Grand, France) JO - Cell. Mol. Biol. (Noisy-le-grand) VL - 49 IS - 2 N2 - The discoveries that activated macrophages produce 1alpha25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3), and that immune system cells express the vitamin D receptor (VDR), suggested that the vitamin D endocrine system influences immune system function. In this review, we compare and contrast how 1alpha,25-(OH)2D3 synthesis and degradation is regulated in kidney cells and activated macrophages, summarize data on hormone receptor function and expression in lymphocytes and myeloid lineage cells, and discuss how locally-produced 1alpha,25-(OH)2D3 may activate a negative feed-back loop at sites of inflammation. Studies of immunity in humans and animals lacking VDR function, or lacking vitamin D, are viewed to gain insight into the immunological functions of the vitamin D endocrine system. The strong associations between poor vitamin D nutrition, particular VDR alleles, and susceptibility to chronic mycobacterial infections, together with evidence that 1alpha,25-(OH)2D3 served as a vaccine adjuvant enhancing antibody-mediated immunity, suggest a model wherein high levels of 1alpha,25-(OH)2D3-liganded VDR transcriptional activity may promote the CD4+ T helper 2 (Th2) cell-mediated and mucosal antibody responses to cutaneous antigens in vivo. We also review a diverse and rapidly growing body of epidemiological, climatological, genetic, nutritional and biological evidence indicating that the vitamin D endocrine system functions in the establishment and/or maintenance of immunological self tolerance. Studies done in animal models of multiple sclerosis (MS), insulin-dependent diabetes mellitus (IDDM), inflammatory bowel disease (IBD), and transplantation support a model wherein the 1alpha,25-(OH)2D3 may augment the function of suppressor T cells that maintain self tolerance to organ-specific self antigens. The recent progress in infectious disease, autoimmunity and transplantation has stimulated a gratifying renaissance of interest in the vitamin D endocrine system and its role in immunological health. SN - 0145-5680 UR - https://www.unboundmedicine.com/medline/citation/12887108/The_immunological_functions_of_the_vitamin_D_endocrine_system_ L2 - https://medlineplus.gov/vitamind.html DB - PRIME DP - Unbound Medicine ER -