Vitamin D is important for the immune system to correctly function (no surprise) – Jan 2024

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Vitamin D and immune system (chapter in a book, PDF behind paywall)

Advances in Food and Nutrition Research March 2024 https://doi.org/10.1016/bs.afnr.2023.12.001
Geoffrey Brown a, Aleksandra Marchwicka b, Ewa Marcinkowska b

The active metabolite of vitamin D 1,25(OH)2D is well known for its role in regulating calcium-phosphate homeostasis of the human body. However, the immunomodulating activity of 1,25(OH)2D has been known for many years. There are numerous reports correlating low vitamin D levels in blood serum with the onset of autoimmune diseases and with the severe course of acute infections. In this chapter, we address the role of 1,25(OH)2D in these diseases, and we discuss the possible mechanisms of action of 1,25(OH)2D in immune cells.

Section snippets
Vitamin D metabolism in brief
Vitamin D, despite being named a “vitamin”, is a steroid hormone (Carlberg, 2014). It is produced by the human body from cholesterol, and its effective concentration is strictly regulated by feedback mechanisms. Vitamin D is produced from 7-dehydrocholesterol in human skin, when exposed to UV light. Activation of vitamin D is controlled by cytochrome P450 mixed-function oxidases (CYPs) and occurs in two steps: 25-hydroxylation followed by 1α-hydroxylation (Prosser & Jones, 2004). The first . . .

Vitamin D and innate immune system
The innate immune system is a combination of chemical messengers, proteins and cells which create the first line of defence against the pathogens that invade the human body. It is evolutionarily the older part of our body’s defence system. For example, toll and toll-like receptors (TLRs), which recognize pathogens, and a prototypic pathway for complement activation and perforin proteins, which attack bacterial membranes, are present in corals, sea anemones and members of the basal phylum. . . .

Vitamin D and acquired immune system
Acquired (adaptive) immunity comprises of B and T cells that recognize specific antigens. These cells recognize a huge variety by means of their receptors: the T cell receptor (TCR) and B cell receptor (BCR; transmembrane immunoglobulin). Due to the process of gene recombination, everyone can produce billions of different TCRs and billions of different BCRs and each T and B cell expresses many copies of just one type of receptor to enable the entire population of T and B cells to recognize a. . . .

Monocytes/macrophages and the influence of 1,25(OH)2D
Human monocytes were among the first of the immune cells that were known to express VDR (Provvedini & Manolagas, 1989). One of the earliest pieces of evidence to support the view that vitamin D has a role in modulating the functionality of these immune cells was the finding that 1,25(OH)2D stimulates the differentiation of monocytic precursors into mature and macrophage-like cells. Vitamin D plays, therefore, a role in the maintenance of monocytes/macrophages (Mangelsdorf, Koeffler, Donaldson,. . . .

Dendritic cells and the influence of 1,25(OH)2D
Dendritic cells (DC) are the most potent APC and, therefore, they play a pivotal role in the initiation of a primary immune response and adaptive immunity against an invading pathogen. They are also important to the maintenance of immunological tolerance to self-antigens by virtue of their ability to regulate the nature of T cell–mediated immune responses (Banchereau, Briere, et al., 2000). DCs are closely related to monocytes and macrophages and like monocytes/macrophages they express the VDR. . . .

Lymphocytes and the influence of 1,25(OH)2D
Both T and B lymphocytes express VDR (Cantorna et al., 2015, Nowak et al., 2020, Provvedini and Manolagas, 1989, Provvedini et al., 1983). And all the cells that are involved in acquired immunity are affected by the action of 1,25(OH)2D. In this regard, the 1,25(OH)2D-mediated actions of importance are orchestrated predominantly by T helper and T regulatory cells. The exact mechanisms are discussed below (in Modes of action of vitamin D in autoimmune diseases).. . . .

Vitamin D and autoimmunity
As considered above, vitamin D is important to the correct functioning of the immune system. Therefore, of further interest are whether a low level of vitamin D influences the risk of developing an autoimmune disease and vitamin D can dampen down immune responsiveness to the benefit of patients. Infectious agents including viruses, bacteria, and other pathogens are presumed to play a major role in initiating or exacerbating autoimmune diseases. The many mechanisms include the pathogen mimicking . . . .

Vitamin D and infections
There are hundreds of publications that suggest a beneficial role of vitamin D in preventing infections, or in the disease outcome (Grant Lahore et al., 2020). Detailed epidemiological data are presented in another chapter of this book. Two infections are the most represented in these publications: influenza and Covid-19. . . .

Final remarks
It is well documented that a normal level of vitamin D is important to the functionality of the immune system regarding the elimination of invading pathogens. Aspects of both the innate and adaptive immune response are subject in many ways to regulation by 1,25(OH)2D. Many immune response genes are regulated by 1,25(OH)2D. Whether there is substantial benefit to be gained from the use of vitamin D to treat inappropriate responsiveness of the immune system, namely the various autoimmune diseases . . . .

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47 of the references

• P.K. Anand et al.– Downregulation of TACO gene transcription restricts mycobacterial entry/survival within human macrophages – FEMS Microbiology Letters (2005)
• B. Beutler – Tlr4: central component of the sole mammalian LPS sensor - Current Opinion in Immunology – (2000)
• J.B. Cowland et al. - hCAP-18, a cathelin/pro-bactenecin-like protein of human neutrophil specific granules - FEBS Letters - (1995)
• A. Doosti-Irani et al. - The effects of vitamin D supplementation on expanded disability status scale in people with multiple sclerosis: A critical, systematic review and metaanalysis of randomized controlled trials - Clinical Neurology and Neurosurgery - (2019)
• S. Ebert et al. - Dose-dependent activation of microglial cells by Toll-like receptor agonists alone and in combination - Journal of Neuroimmunology - (2005)
• G. Ferrari et al. - A coat protein on phagosomes involved in the intracellular survival of mycobacteria - Cell - (1999)
• T. Ganz - Defensins: Antimicrobial peptides of vertebrates - Comptes Rendus Biologies - (2004)
• M.G. Gutierrez et al. - Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages - Cell - (2004)
• K.Y. Helmy et al. - CRIg: A macrophage complement receptor required for phagocytosis of circulating pathogens - Cell - (2006)
• G. Hemmrich et al. - The evolution of immunity: A low-life perspective - Trends in Immunology - (2007)
• D. Heras-Sandoval et al. - The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration - Cellular Signalling - (2014)
• M. Hewison - Vitamin D and the intracrinology of innate immunity - Molecular and Cellular Endocrinology - (2010)
• M. Hewison et al. - Vitamin D and barrier function: a novel role for extra-renal 1 alpha-hydroxylase - Molecular and Cellular Endocrinology - (2004)
• D.D. Hickstein et al. - Isolation and characterization of the receptor on human neutrophils that mediates cellular adherence - The Journal of Biological Chemistry - (1987)
• M. Holick - Vitamin D and bone health - The Journal of Nutrition - (1996)
• H. Korf et al. - 1,25-Dihydroxyvitamin D3 curtails the inflammatory and T cell stimulatory capacity of macrophages through an IL-10-dependent mechanism - Immunobiology - (2012)
• M. Kracht et al. - Transcriptional and post-transcriptional control of gene expression in inflammation - Cytokine - (2002)
• M. Akkaya et al. - B cell memory: Building two walls of protection against pathogens - Nature Reviews. Immunology - (2020)
• K.S. Aljabri et al. - Glycemic changes after vitamin D supplementation in patients with type 1 diabetes mellitus and vitamin D deficiency - Annals of Saudi Medicine - (2010)
• B. Alosaimi et al. - Complement anaphylatoxins and inflammatory cytokines as prognostic markers for COVID-19 severity and in-hospital mortality - Frontiers in Immunology - (2021)
• A.N. Ananthakrishnan et al. - Normalization of plasma 25-hydroxy vitamin D is associated with reduced risk of surgery in Crohn’s disease - Inflammatory Bowel Diseases - (2013)
• A. Aranda et al. - Nuclear hormone receptors and gene expression - Physiological Reviews - (2001)
• E.V. Arkema et al. - Exposure to ultraviolet-B and risk of developing rheumatoid arthritis among women in the Nurses’ Health Study - Annals of the Rheumatic Diseases - (2013)
• J. Banchereau et al. - Immunobiology of dendritic cells - Annual Review of Immunology - (2000)
• J. Banchereau et al. - Dendritic cells and the control of immunity - Nature - (1998)
• B. Bertani et al. - Function and biogenesis of lipopolysaccharides - EcoSal Plus - (2018)
• P. Bhavsar et al. - Relative corticosteroid insensitivity of alveolar macrophages in severe asthma compared with non-severe asthma - Thorax - (2008)
• G. Bizzaro et al. - Vitamin D and autoimmune diseases: Is vitamin D receptor (VDR)
• polymorphism the culprit? - The Israel Medical Association Journal: IMAJ - (2017)
• C. Bizzarri et al. - No protective effect of calcitriol on beta-cell function in recent-onset type 1 diabetes: The IMDIAB XIII trial - Diabetes Care - (2010)
• A. Boonstra et al. - 1α,25-Dihydroxyvitamin D3 has a direct effect on naive CD4+ T cells to enhance the development of Th2 cells - The Journal of Immunology - (2001)
• J.J. Cannell et al. - Epidemic influenza and vitamin D - Epidemiology & Infection - (2006)
• M. Cantorna et al. - Vitamin D and 1,25(OH) 2D regulation of T cells - Nutrition (Burbank, Los Angeles County, Calif.) - (2015)
• C. Carlberg - The physiology of vitamin D-far more than calcium and bone - Frontiers in Physiology - (2014)
• C. Carlberg et al. - Primary vitamin D target genes allow a categorization of possible benefits of vitamin D3 supplementation - PLoS One - (2013)
• N. Charoenngam et al. - Immunologic effects of vitamin D on human health and disease - Nutrients - (2020)
• Y. Chen et al. - 1,25-Dihydroxyvitamin D promotes negative feedback regulation of TLR signaling via targeting microRNA-155-SOCS1 in macrophages - Journal of Immunology - (2013)
• N. Chouaki Benmansour et al. - Complement cascade in severe forms of COVID-19: Recent advances in therapy - European Journal of Immunology - (2021)
• T. Christides - Vitamin D and risk of type 2 diabetes - BMJ (Clinical Research ed.) - (2022)
• G.S. Cooper et al. - Occupational and environmental exposures and risk of systemic lupus erythematosus: Silica, sunlight, solvents - Rheumatology (Oxford, England) - (2010)
• R.Q. Cron et al. - Cytokine storm syndrome - Annual Review of Medicine - (2023)
• D. D’Ambrosio et al. - Inhibition of IL-12 production by 1,25-dihydroxyvitamin D3. Involvement of NF-kappaB downregulation in transcriptional repression of the p40 gene - The Journal of Clinical Investigation - (1998)
• A. Daneshkhah et al. - The possible role of vitamin D in suppressing cytokine storm and associated mortality in COVID-19 patients - medRxiv - (2020)
• A. Daneshkhah et al. - Evidence for possible association of vitamin D status with cytokine storm and unregulated inflammation in COVID-19 patients - Aging Clinical and Experimental Research - (2020)
• W. Dankers et al. - Vitamin D in autoimmunity: Molecular mechanisms and therapeutic potential - Frontiers in Immunology - (2016)
• F.P. De Heredia et al. - Obesity, inflammation and the immune system - The Proceedings of the Nutrition Society - (2012)
• H.F. DeLuca et al. - UVB radiation, vitamin D and multiple sclerosis - Photochemical & Photobiological Sciences: Official Journal of the European Photochemistry Association and the European Society for Photobiology - (2017)
• P. Delves et al. - Roitt’s essential immunology - (2017)
• H. Derakhshandi et al. - Preventive effect of vitamin D3 supplementation on conversion of optic neuritis to clinically definite multiple sclerosis: A double blind, randomized, placebo-controlled pilot clinical trial - Acta Neurologica Belgica - (2013)
• D. Dharmapalan - Influenza - The Indian Journal of Pediatrics - (2020)
• R. Dobson et al. - The month of birth effect in multiple sclerosis: Systematic review, meta-analysis and effect of latitude - Journal of Neurology, Neurosurgery, and Psychiatry - (2013)

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VitaminDWiki – Immunity category contains

263 items in Immunity category

    see also

Virus category listing has 1365 items along with related searches

Overview Influenza and vitamin D
Vitamin D helps both the innate and adaptive immune systems fight COVID-19 – Jan 2022
Vitamin D aids the clearing out of old cells (autophagy) – many studies
600,000 IU of Vitamin D (total) allowed previously weak immune systems to fight off a virus antigen - Nov 2020
Search for treg OR "t-cell" in VitaminDWiki 1440 items as of Jan 2020
228 VitaminDWiki pages contained "infection" in title (June 2024)
Search VitaminDWik for BACTERIA in title 25 items as of Aug 2019
Vitamin D and the Immune System – chapter Aug 2019
7X less risk of influenza if Vitamin D levels higher than 30 ng – Oct 2017
Common cold prevented and treated by Vitamin D, Vitamin C, Zinc, and Echinacea – review April 2018
Vitamin D improves T Cell immunity – RCT Feb 2016
Immune system - great 11-minute animated video - Aug 2021
   Only the brain is more complex, nothing about Vitamin D
18 titles in VitaminDWiki contained INNATE or ADAPTIVE as of Jan 2023
Increasing publications on vitamin D and Infection

48 studies are in both Immunity and Virus categories

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201+ VitaminDWiki Immunity pages have VITAMIN in the title

This list is automatically updated

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VitaminDWiki – Autoimmune category contains

• 197 items in Autoimmune category
• Vitamin D and   MS    Asthma    RA    Diabetes    Gut   Allergy    Hay Fever    Lupus    Psoriasis
• Predicted 95% autoimmune cured by HIGH-DOSE vitamin D - 2014
• 10% of the UK have Autoimmune Diseases - Lancet May 2023 PDF is behind a paywall
  • Increase in 20 years : coeliac disease 2.19 X. Sjogren's syndrome 2.09, and Graves' disease 2.07
  • All 43 references are FREE on-line
• Autoimmune diseases fought by Vitamin D, especially if have more than 40 ng – Sept 2022
• The BEST Nutrient for Autoimmune Conditions (Vitamin D) - video May 2022
• The number 1 Deficiency behind All Autoimmune Diseases (Vitamin D) video - Dec 2023
• Autoimmune disease clusters run in families having low D
• How Vitamin D reduces inflammation, improves immunity and fights autoimmunity – review Dec 2018
• 120 doctors and 20,000 MS patients using high dose Vitamin D Dec 2018
• Vitamin D has treated Multiple Sclerosis and autoimmune diseases for 16 years – Coimbra April 2018
• Vitamin D Receptor is associated in over 58 autoimmune studies
• More autoimmune disease if higher pollution or lower UVB - Feb 2023
• Many autoimmune diseases associated with low vitamin D or poor Vit D genes – July 2019
  

See also web: consensus that ~50 diseases are autoimmune, ~50 more are suspected: