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

Created March 2024

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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