Vitamin D deficiency leads to autoimmune disease

[메디컬투데이=최재백 기자] Research has shown that vitamin D deficiency causes T cells to overreact to healthy substances.

Research results have been published in ‘Science Advances’ showing that vitamin D deficiency causes T cells to over-stimulate immune defenses against healthy substances.

Vitamin D is essential for bone health as well as normal immune function. Vitamin D deficiency is associated with an increased risk of developing autoimmune diseases such as type 1 diabetes, but the causal mechanism is not clearly known.

Autoimmune diseases can occur when T cells, a type of white blood cell, cannot distinguish healthy cells from unhealthy or infected cells.

First, T cells stimulate immune responses that target microorganisms, participate in the process of eliminating infected cells and cancer cells, and play a very important role in regulation of autoimmune responses.

In order for T cells to work, they must be able to distinguish body proteins, ie self-antigens, from foreign proteins T cell immune tolerance refers to the ability of T cells to recognize self-antigens and not to stimulate an immune response that targets normal It is called T-cell tolerance.

T cell tolerance occurs when T cells mature from bone marrow derived cells within the thymus, located in the upper chest. At this time, T cell precursors that do not give an immune response to self-antigens but stimulate an active immune response to foreign proteins are selected in the cortex, the outer part of the thymus.

Subsequently, autoreactive T cells that trigger an immune response against normal body tissues are removed from the medulla in the center of the thymus through a process of negative selection.

Each epithelial cell of the thymic medulla expresses some genes that are included in the human genome, and together, it can express most of the genes that make up the genome. In other words, almost all self-antigens can be expressed in the thymus, thus conferring T-cell tolerance to almost all tissues in the body and preventing re- autoimmune disorders.

At the same time, since the receptor for the active form of vitamin D is expressed in the thymus, vitamin D deficiency often causes the thymus to shrink in size.

In addition, according to the research team’s previous research, vitamin D is very important in inducing T-cell immune tolerance and preventing autoimmune responses by increasing the expression of self-regulatory genes. -protection (Attention).

The research team explained that vitamin D affects the development of T cells in the thymus from an early age as well as the tolerance of T cell immunity.

Therefore, the research team investigated the way in which vitamin D changes T cell function and the effect it has on the risk of developing autoimmune diseases.

Vitamin D is converted to its biologically active form by the enzyme Cyp27b1 to understand the effect of vitamin D on immune function, the research team used mice engineered to have genetic mutations in the two gene pairs that expression of Cyp27b1.

In other words, the genetically modified mice could not produce active vitamin D, so the size of the thymus and the number of T cells in the blood decreased, mimicking a situation in which the gland thymus grows faster.

In addition, a lower proportion of thymic medullary epithelial cells expressed the Aire gene than normal control mice, and the number of medullary epithelial cells that would present self-antigens for T cell development was also reduced.

The research team noted that markers suggesting ‘reduced T cell immune tolerance’ increased in mice whose thymus glands had been altered so that they could not produce active vitamin D, and they explained that this was due to an increase in T cells that trigger a strong immune response. targeting self-antigens did ee

They reported that autoantibody levels were particularly higher in certain tissues (lungs and salivary glands) of genetically modified mice in late adulthood.

They found abnormalities in the medullary thymic epithelial cells required for the T cell ‘negative selection’ process, and thus the ‘negative selection’ process in mice engineered with the associated gene the enzyme Cyp27b1, which converts vitamin D to its active form. himself.

They concluded that vitamin D is essential for normal thymic development and function by producing autoreactive T cells.

Medical Today Reporter Jaebaek Choi ([email protected])

[저작권자ⓒ 메디컬투데이. 무단전재-재배포 금지]