Vitamin D deficiency: Does it affect the risk of autoimmune disease?

• Vitamin D deficiency, especially in early life, is associated with an increased risk of autoimmune conditions, such as type 1 diabetes.
• Autoimmune diseases can be caused by the failure of T cells, a type of white blood cell, to distinguish unhealthy or infected cells from healthy ones.
• A new study conducted in mice shows that a lack of vitamin D leads to the development of T cells that produce an overreaction of the body against healthy cells.
• These effects of vitamin D on T cell development may be mediated by its effects on thymus cells, a gland that stimulates T cell growth and response.
• This study sheds light on how vitamin D deficiency may increase the risk of autoimmune conditions.

Vitamin D is important not only for bone health but also for normal immune function. Vitamin D deficiency is associated with an increased risk of autoimmune diseases, but the mechanisms underlying this association are not well understood.

A new study published in Advances in Science now shows that disrupting a key enzyme involved in the conversion of vitamin D to its biological form can negatively affect T cell development.

This results in an overproduction of T cells that can attack the body’s own cells, a phenomenon known as auto reactivity.

This study – carried out in a mouse model – also showed that this increase in autoreactive T cells was mediated by the negative effects of vitamin D deficiency on thymus cells, a special organ that stimulates the growth of T cells and their ability to distinguish between healthy and infected or foreign cells.

Study author John White, PhD, professor of physiology at McGill University in Montreal, Canada, told Medical News Today:

“Our research has shown that vitamin D is necessary for normal thymic development, “removal” of autonomous T cells, and thymic longevity.”

In addition to its role in bone health, vitamin D also modulates the function of the immune system. For example, personal information move the relationship between vitamin D deficiency and a higher risk of autoimmune diseases that involve the production of an immune response against the body’s own cells.

T cells, a special type of white blood cell, plays an important role in controlling this autoimmune reaction. T cells help facilitate the body’s immune response against pathogens and the elimination of potentially infected or cancerous cells.

These functions of T cells depend on their ability to distinguish the body’s proteins, known as self-proteins or self-antigens, from foreign proteins. The ability of T cells to recognize antigens and avoid an immune response is known as T-cell tolerance.

T cell tolerance occurs during the development of T cells from early marrow-derived cells in the thymus, a gland located in the upper part of the chest.

Specifically, T-cell tolerance involves the selection of T-cell precursors that produce strong responses against foreign proteins but not antigens.

During the early stages of T cell development, a positive selection of precursor T cells capable of producing strong responses against foreign antigens occurs in the outer thymus. called the cortex.

The next stages of T cell development occur in the central part of the thymus called the medulla. T cells that produce responses to healthy body cells are removed from the medulla in a process called negative selection.

Epithelial cells in the medulla produce a subset of the human genome, which together produce the majority of genes in the genome.

Expression of almost all of the proteins in the thymus results in T cell tolerance to all body cells.

The active form of vitamin D is produced in the thymus, and vitamin D deficiency is associated with a decrease in the size of the thymus.

Clearly, the authors’ previous work has shown that vitamin D can enhance the expression of the type of autoimmune regulator (Aire), so it is important for the development of T-cell tolerance and the prevention of autoimmune reactions.

Development of the T cell population in the thymus during human life is completed at puberty.

This, together with the strong influence of vitamin D on immune function in early life, suggests that vitamin D may stimulate the development of T cells in the thymus in early life to induce tolerance. of T cells.

In the current study, the researchers examined the ways in which vitamin D can alter the activity of T cells in early life, and later, the risk of autoimmune conditions.

Vitamin D is converted to its biological form in the body by the enzyme Cyp27b1. To understand the effect of vitamin D on immune function, researchers used a genetically engineered mouse model to carry a mutation in two copies of the gene that produces Cyp27b1, which results in the ability to produce the type active vitamin D.

These mice lacking biologically active vitamin D showed a reduced size of the thymus and a lower number of T cells in the blood, indicating accelerated aging of the thymus.

These mice also had a smaller proportion of epithelial cells in the medulla expressing the autoimmune regulator gene (Aire) than wild-type control mice.

In addition, there was a reduction in the number of medullary epithelial cells in the thymus that present self-antigens to developing T cells. A previous study showed that the number of medullary epithelial cells that express a particular antigen is related to the degree of T cell tolerance for that antigen.

These changes in the thymus of mice unable to produce biologically active vitamin D were accompanied by an increase in markers of T cell tolerance, i.e., an increase in T cells that produce a strong response to antigens.

Finally, these mice also show increased levels of autoantibodies in certain tissues, such as the lungs and salivary glands, in adulthood. However, such high levels of autoantibodies were not present in other cells.

Older mice, but not young adults, lacking active vitamin D also showed glucose (blood sugar) control.

Summarizing these findings, White noted that: “We found that the development of epithelial cells in the thymus that is important for the negative selection of T cells was impaired in the mutant mice. Furthermore , the negative selection of T cells itself was disrupted.”

“The aged mice also developed immune symptoms and, in some cases, type 1 diabetes,” he said. “Interestingly, we found that, in the absence of an active form of vitamin D, thymic aging was greatly accelerated,” which may increase the risk of autoimmune conditions.