In a recent review published in the journal Dr nutrientsResearchers have explored the role of a person’s immunocompetence in their responsiveness to vitamin D.
They discussed the modulation of immunocompetence through the epigenetic programming function of the vitamin D receptor (VDR) and its ligand and highlighted the effect of aging on immunocompetence.
Study: Vitamin D and aging: the central role of immunocompetence. Image credit: Iryna Imago/Shutterstock.com
Vitamin D plays an important role in bone health by regulating calcium homeostasis and preventing conditions such as rickets and osteomalacia. However, its effects on immunity extend beyond this function.
Vitamin D deficiency, associated with modern lifestyle factors such as limited sun exposure, affects the endogenous production of active vitamin D metabolites.
Inactive vitamin D3 In the liver and kidney it is converted to active 1,25(OH)2D3, which acts as a hormone and affects various tissues. Notably, various cells including the innate immune system can produce 1,25(OH)2D3 locally, contributing to auto- and paracrine effects. This compound acts as a high affinity ligand for VDR, regulating the expression of numerous genes.
Vitamin D status, indicated by serum 25(OH)D3 levels, classifies individuals into deficient, insufficient, or sufficient groups. Vitamin D responsiveness varies among humans due to genetic and epigenetic factors influencing the molecular response.
Low responders, comprising about 25% of the population, may have increased susceptibility to diseases related to compromised immunity. VDR-based modulation of immunocompetence may contribute to aging and reduce the risk of age-related diseases.
The present review provides insight into the immunomodulatory function of vitamin D and its effects on various health aspects beyond bone metabolism.
Vitamin D signaling
VDR specifically binds to genomic DNA, recognizing the motif RGKTSA. In complex with retinoid X receptor (RXR), VDR preferentially binds to direct repeat sequences in euchromatin. Various “pioneer factors” assist VDR in opening chromatin, which is crucial for efficient binding.
Chromatin accessibility and VDR binding can be assessed using next-generation sequencing technologies, particularly in mononuclear peripheral blood cells, including ChIP-seq (chromatin immunoprecipitation sequencing) and ATAC-seq (assay for transposase-accessible chromatin using sequencing).
Genomic regions of vitamin D target genes exhibit changes in chromatin accessibility and VDR binding after vitamin D3 complement
Enhancer and transcription start site regions, even at a significant linear distance, can interact through DNA looping within the same topologically associating domain, influencing gene expression.
The genomic actions of VDR involve protein-protein interactions with the Mediator complex and RNA polymerase II, which affect transcription. Vitamin D also exerts epigenomic effects, altering DNA methylation, histone modifications and chromatin organization, dynamically shaping the cell’s epigenetic landscape.
These genomic and epigenomic effects contribute to the modulatory role of vitamin D in hematopoiesis and immunocompetence, affecting both human immune cells. in vitro And alive.
Epigenetic programming of immune cells
During embryonic and adult cellular differentiation, stem and progenitor cells undergo epigenetic programming, which ultimately determines the function of individual cells. 1,25(OH)2D3 plays an important role in this process, influencing hematopoiesis and immune cell differentiation.
Hematopoietic stem cells (HSCs) differentiate into various blood and immune cell types and 1,25(OH)2D3 regulates fetal HSC numbers.
Various transcription factors influenced by vitamin D drive the differentiation of myeloid progenitor cells into granulocytes and monocytes. Vitamin D also differentiates monocytes into dendritic cells and macrophages.
Epigenetic programming by vitamin D contributes to innate immune cell adaptation, modulating the response to infection, inflammation and disease.
Variability of vitamin D status and inter-individual response indices influence epigenetic programming of monocytes and derived cells, emphasizing potential for optimized vitamin D3 Supplements to support proper immune cell epigenetics and overall immunocompetence. However, more research is needed to fully validate this idea.
The immune system declines during aging
Molecular damage accumulates with aging, leading to cell dysfunction and weakened organs. Immunocompetence, crucial for an appropriate immune response, declines with age, increasing susceptibility to infection and disease.
The thymus atrophies, reduces T-cell production and becomes “inflammatory”. However, interindividual differences exist, and some individuals may exhibit relatively high resistance.
Low immunity is associated with accelerated aging and increased disease risk. Vitamin D adequacy may protect against cancer by preserving the immune system.
Adequate vitamin D levels can stabilize the immune system, protect against disease, and contribute to healthy aging by mitigating various hallmarks of aging, including inflammation and cellular stress.
In conclusion, the active form of vitamin D plays an important role in modulating the epigenome of immune cells, especially in monocytes.
The observed associations between vitamin D deficiency, increased disease risk, and accelerated aging can be attributed to decreased immunocompetence.
Considering individual response, a precautionary daily vitamin D3 dose of 1 µg (40 IU)/kg body mass is recommended, exceeding the usual recommendations but remaining within safe limits for strengthening immunocompetence. Researchers emphasize personalized vitamin D supplementation to protect against common diseases and promote healthy aging.