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Cited by 230Vitamin D Research StudiesImmune responses and vaccinationsImmune Response and Inflammation

Vitamin D and the intracrinology of innate immunity

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Hewison, Martin·2010·Molecular and Cellular Endocrinology
DOI 10.1016/j.mce.2010.02.013PMC PMC2854233
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Abstract

An immunomodulatory role for vitamin D was first proposed more than 25 years ago, based on two salient observations. Firstly it was shown that monocytes/macrophages from patients with the granulomatous disease sarcoidosis constitutively synthesize the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)(2)D) from precursor 25-hydroxyvitamin D (25OHD). Secondly, the receptor for 1,25(OH)(2)D (vitamin D receptor, VDR) is detectable in activated, proliferating lymphocytes. These observations suggested a mechanism whereby 1,25(OH)(2)D produced by monocytes could act upon adjacent T-cells or B-cells, but the impact of such a system on normal immune regulation was uncertain. Indeed, it is only in recent years that a much clearer picture of the role of vitamin D as a determinant of immune responsiveness has emerged. Two new concepts have prompted this change. Firstly studies of innate immunity have shown that intracrine induction of antimicrobial activity by vitamin D is a pivotal component of monocyte/macrophage response to infection. Secondly, it is now clear that sub-optimal vitamin D status is a common feature of many populations throughout the world, with the potential to compromise monocyte/macrophage metabolism of 25OHD and subsequent actions of 1,25(OH)(2)D. The current review details these new developments with specific reference to the metabolic and signaling mechanisms associated with innate immune regulation by vitamin D and implications for human disease.

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  • The most biologically active vitamin D metabolite is 1,25-dihydroxyvitamin D3, which is synthesized locally in the skin and systemically after skin exposure to sunlight.

    “The most biologically active vitamin D metabolite is 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], which is synthesized locally in the skin and systemically after skin exposure to sunlight [84].”

    From Molecular Mechanisms of UV-Induced Apoptosis and Its Effects on Skin Residential Cells: The Implication in UV-Based Phototherapy (2013) · cites this paper as [84]

    The Introduction identifies 1,25(OH)2D as the active form of vitamin D and describes its systemic synthesis in the kidney. Section 5 describes localized production in skin keratinocytes under conditions of epidermal wounding. The cited passages do not establish that sunlight exposure triggers either the local or systemic synthesis of 1,25(OH)2D. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Activation of Toll-like receptor 1 and TLR2 by tuberculosis enhances 1α-hydroxylase expression, production of antimicrobial peptide cathelicidin, and induction of tolerogenic dendritic cells and T cells.

    “Activation of Toll-like receptor 1 (TLR1) and TLR2 by tuberculosis enhances 1α-hydroxylase expression, the enzyme mediates the synthesis of 1,25(OH)2D3, production of antimicrobial peptide cathelicidin [87], and induction of tolerogenic DCs and T cells [60,84].”

    From Molecular Mechanisms of UV-Induced Apoptosis and Its Effects on Skin Residential Cells: The Implication in UV-Based Phototherapy (2013) · cites this paper as [84]

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Authors
Hewison, M.
Affiliations
University of California, Los Angeles (US)
Corresponding author
Hewison, Martin
ORCID
Hewison, Martin
Venue
Molecular and Cellular Endocrinology
Publisher
Elsevier BV
Published
2010-06
Volume
321
Issue
2
Pages
103-111
ISSN
0303-7207 (ISSN-L)
DOI
10.1016/j.mce.2010.02.013
PMC
PMC2854233
OpenAlex
W2016323086
Cited by
230
References
1
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FWCI
2.32
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Molecular and Cellular Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
Funders
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR050626)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
vitamin D, intracrine signaling, innate immunity, vitamin D receptor, 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, monocytes, macrophages, antimicrobial activity, immune regulation, vitamin D status, sarcoidosis, lymphocytes
MeSH terms
Humans, Immunity, Innate, Vitamin D, Receptors, Calcitriol

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