A new mice model study has highlighted how vitamin D deficiency in early life may increase the risk of autoimmune diseases, including type 1 diabetes. Published in Science Advances, the research led by Artusa and colleagues investigated the mechanisms by which low vitamin D levels might increase the likelihood of autoimmune conditions. Using a mouse model, the researchers observed that vitamin D deficiency can lead to the development of autoreactive T cells, which attack the body’s tissues rather than foreign invaders, thereby undermining immune tolerance.
The immune system’s capacity to distinguish between self and foreign proteins is a critical function of T cells. This “training” occurs in the thymus, where immature T cells undergo a selection process to avoid self-reactivity. In the thymus, positive selection preserves T cells that respond to foreign antigens, while negative selection in the medulla removes T cells that might mistakenly target the body’s own proteins. Research indicates that vitamin D is crucial in supporting this selection by regulating the expression of the autoimmune regulator (Aire) gene, essential for T cell tolerance. Insufficient vitamin D weakens this mechanism, potentially allowing autoreactive T cells to develop and attack the body’s cells.
To explore this effect, Artusa and colleagues studied genetically modified mice that lacked the enzyme Cyp27b1, necessary to convert vitamin D into its active form. These mice exhibited reduced thymus size, fewer circulating T cells, and signs of accelerated thymic aging. Researchers noted that these mice had fewer Aire-expressing epithelial cells in the thymus, essential for presenting self-antigens to developing T cells, resulting in a lower capacity for T cell tolerance. This reduction in thymic function was associated with increased numbers of self-reactive T cells.
In addition to observing thymic aging, the study found that vitamin D deficiency increased the presence of autoantibodies in specific tissues, such as the lungs and salivary glands, in older mice. These mice also showed impaired glucose regulation in late adulthood, suggesting a potential link to early type 1 diabetes symptoms. This evidence concurs the critical role of vitamin D in supporting the immune system’s ability to tolerate self-antigens and prevent autoimmune reactions, particularly in early life.
A review by Sanlier and Coskun further supports these findings, noting that vitamin D deficiency is linked to immune dysregulation, which can increase susceptibility to autoimmune and infectious diseases. They emphasize that low serum vitamin D levels are associated with a wide range of immune-mediated conditions. While vitamin D supplementation may help reduce disease severity, they call for further randomized trials to establish optimal dosing and clarify the role of vitamin D in immune health.
This study underscores the importance of vitamin D in T cell development and immune tolerance, particularly during early life. By helping to regulate thymic function and prevent the emergence of autoreactive T cells, adequate vitamin D levels may reduce the risk of autoimmune diseases. These findings highlight the need to maintain sufficient vitamin D levels during early life to support immune health and lower the chances of autoimmune conditions later in life.
References
- Artusa P, Nguyen Yamamoto L, Barbier C, Valbon SF, Aghazadeh Habashi Y, Djambazian H, et al. Skewed epithelial cell differentiation and premature aging of the thymus in the absence of vitamin D signaling. Sci Adv. 2024 Sep 27;10(39):eadm9582.
- Sanlier N, Guney-Coskun M. Vitamin D, the immune system, and its relationship with diseases. Egyptian Pediatric Association Gazette. 2022 Oct 17;70(1):39.