ISLAMABAD: A lack of vitamin D, particularly in early life, is associated with a heightened likelihood of autoimmune diseases, such as type 1 diabetes. Autoimmune disorders can result from the inability of T cells—a kind of white blood cell—to differentiate between healthy cells and those that are unhealthy or infected.Healthy Competition and Market Repair Key to Industry Growth.Aamir Ibrahim

A recent study conducted on mice demonstrates that vitamin D deficiency resulted in the formation of T cells that trigger an overactive immune response against healthy tissues. The influence of vitamin D on T cell development is likely mediated by its effects on thymic cells, which play a key role in T cell maturation and responses.

This research outlines a mechanism through which vitamin D deficiency may elevate the risk of autoimmune disorders. Vitamin D is vital not only for bone health but also for proper immune function. Although there is a recognized connection between vitamin D deficiency and a greater risk of autoimmune diseases, the underlying processes remain poorly understood.

A new study published in Science Advances indicates that disrupting a crucial enzyme responsible for converting vitamin D into its active form can adversely affect T cell development. This disruption leads to the excessive generation of T cells capable of attacking the body’s own tissues, a phenomenon known as auto-reactivity. The study, which utilized a mouse model, also revealed that the rise in autoreactive T cells was influenced by the detrimental effects of vitamin D deficiency on thymic cells, the specialized organ crucial for T cell maturation and their ability to differentiate between healthy and infected or foreign cells.

John White, PhD, a physiology professor at McGill University in Montreal, Canada, explained to Medical News Today: “Our research revealed that vitamin D is essential for normal thymic development, optimal elimination of self-reactive T cells, and thymic longevity.”

What is the role of T cells in immune system regulation? In addition to its importance for bone health, vitamin D also influences immune system functionality. Observational data suggest a correlation between vitamin D deficiency and an increased risk of autoimmune diseases characterized by an immune response against the body’s own tissues. T cells, a specialized category of white blood cells, are pivotal in regulating this autoimmune response. They assist in orchestrating an immune reaction against pathogens and eliminating potentially infected or cancerous cells.

The effectiveness of T cells hinges on their ability to recognize the body’s own proteins, termed self-proteins or self-antigens, distinguishing them from foreign proteins. This recognition capability is referred to as T-cell tolerance. T-cell tolerance develops during the maturation of T cells from progenitor cells derived from bone marrow within the thymus, a gland located in the upper chest.

Specifically, T-cell tolerance entails the selection of T-cell precursors that mount a strong response against foreign proteins but not against self-antigens. In the initial phases of T cell development, precursor T cells capable of producing robust reactions against foreign antigens undergo positive selection in the thymic cortex. The following stages of T cell development occur in the medulla, the central area of the thymus, where T cells responding to the body’s own healthy tissues are eliminated through a process known as negative selection.

How does vitamin D influence T-cell function? Subpopulations of epithelial cells in the medulla express a portion of the genes within the human genome, collectively representing most genes. The expression of nearly all self-proteins in the thymus facilitates T cell tolerance towards the body’s tissues. The receptor for the active form of vitamin D is present in the thymus, and a deficiency in vitamin D correlates with a reduced thymic size.

Importantly, prior research indicated that vitamin D enhances the expression of the autoimmune regulator (Aire) gene, which is essential for T-cell tolerance development and the prevention of autoimmune responses. The formation of the T cell population in the thymus occurs throughout an individual’s life and is typically completed by puberty. This, along with vitamin D’s pronounced impact on immune function during early life, implies that vitamin D may influence T cell development in the thymus early in life, thereby affecting T cell tolerance.

What is the connection between vitamin D and autoimmune conditions? In this study, researchers explored the mechanisms through which vitamin D potentially regulates T cell function in early life and, in turn, the risk of autoimmune diseases. Vitamin D is converted into its biologically active form by the enzyme Cyp27b1. To investigate the effects of vitamin D on immune function, the researchers utilized a mouse model genetically modified to lack the enzyme, thus rendering them incapable of producing the active form of vitamin D.

These mice, devoid of biologically active vitamin D, exhibited reduced thymic size and fewer T cells in the bloodstream, indicating accelerated thymic aging. They also demonstrated a smaller proportion of epithelial cells in the medulla expressing the Aire gene compared to wild-type mice. Additionally, there was a decline in the number of medullary epithelial cells in the thymus responsible for presenting self-antigens to developing T cells. Previous research indicated a correlation between the quantity of medullary epithelial cells presenting a specific self-antigen and the degree of T cell tolerance to that antigen.

The alterations in the thymus of mice unable to synthesize biologically active vitamin D were accompanied by an uptick in markers indicative of diminished T cell tolerance, specifically an increase in T cells that react strongly to self-antigens. Finally, these mice also exhibited elevated levels of autoantibodies in certain tissues, such as the lungs and salivary glands, during late adulthood, although such heightened levels were absent in other tissues.

Could vitamin D deficiency raise the risk of type 1 diabetes? Older mice lacking active vitamin D, unlike younger ones, displayed compromised glucose regulation. Summarizing these findings, White noted: “We discovered that the development of epithelial cell populations in the thymus, crucial for negative T cell selection, was hindered in mutant mice. Furthermore, negative T cell selection itself was compromised. Aging mutant mice also exhibited signs of autoimmunity and, in some instances, type 1 diabetes. Interestingly, we found that, in the absence of the active form of vitamin D, thymic aging was significantly accelerated, which could further heighten the risk of autoimmune disorders.”