Summary: A recent study found that vitamin D deficiency during childhood accelerates the aging of the thymus, a crucial organ in training immune cells. As the thymus ages, it becomes less effective at filtering out cells that could mistakenly attack the body's own tissues, increasing the risk of autoimmune diseases like type 1 diabetes.
This research highlights the importance of ensuring children get adequate vitamin D, especially during the "vitamin D winter" months when sunlight can't provide enough. The findings could inform new strategies to prevent autoimmune conditions by focusing on early vitamin D intake.
As Canadians brace for "vitamin D winter" -- months when the sun's angle is too low to produce the vitamin in the skin -- a McGill University study explains why vitamin D deficiency early in life is associated with a higher risk of autoimmune diseases.
During childhood, the thymus helps train immune cells to distinguish between the body's own tissues and harmful invaders. A vitamin D deficiency at that stage of life causes the thymus to age more quickly, the researchers discovered.
The study is published in the journal Science Advances.
"An aging thymus leads to a 'leaky' immune system," said lead author John White, a Professor in and Chair of McGill's Department of Physiology.
"This means the thymus becomes less effective at filtering out immune cells that could mistakenly attack healthy tissues, increasing the risk of autoimmune diseases like type 1 diabetes."
He noted that researchers have known for years that vitamin D helps the body absorb calcium for strong bones, and that more recent research has discovered its crucial role in regulating the immune system.
"Our findings bring new clarity to this connection and could lead to new strategies for preventing autoimmune diseases," he said.
Although the research was conducted with mice, the findings are relevant to human health because the thymus functions similarly in both species, White added.
The findings highlight the importance of adequate vitamin D intake, especially for children.
"In places like Montreal, where we stop making the vitamin from sunlight between late fall and early spring, supplementation is key," said White.
"If you have a young child, it's important to consult with your health-care provider to ensure they're getting enough."
The breakthrough builds on a 2001 Finnish study, which followed more than 10,000 children. It found that children who were supplemented early in life with vitamin D had up to a five-fold-lower risk of developing type 1 diabetes later in life.
Finland, with its long periods of vitamin D winter, served as an ideal case study to learn more about the nutrient's many roles, said White.
In the McGill study, researchers used mice that couldn't produce vitamin D to examine how the deficiency affected the thymus, employing cell analysis and gene sequencing to see how it impacts the immune system.
In future studies, White hopes to explore how vitamin D affects the human thymus, something he notes has not been done before.
Author: Keila DePape
Source: McGill University
Contact: Keila DePape - McGill University
Image: The image is credited to Neuroscience News
Original Research: Open access.
"Skewed epithelial cell differentiation and premature aging of the thymus in the absence of vitamin D signaling" by Patricio Artusa et al. Science Advances
Abstract
Skewed epithelial cell differentiation and premature aging of the thymus in the absence of vitamin D signaling
Central tolerance of thymocytes to self-antigen depends on the medullary thymic epithelial cell (mTEC) transcription factor autoimmune regulator (Aire), which drives tissue-restricted antigen (TRA) gene expression.
Vitamin D signaling regulates Aire and TRA expression in mTECs, providing a basis for links between vitamin D deficiency and autoimmunity. We find that mice lacking Cyp27b1, which cannot produce hormonally active vitamin D, display profoundly reduced thymic cellularity, with a reduced proportion of Aire mTECs, attenuated TRA expression, and poorly defined cortical-medullary boundaries.
Markers of T cell negative selection are diminished, and organ-specific autoantibodies are present in knockout (KO) mice. Single-cell RNA sequencing revealed that loss of Cyp27b1 skews mTEC differentiation toward Ccl21 intertypical TECs and generates a gene expression profile consistent with premature aging. KO thymi display accelerated involution and reduced expression of thymic longevity factors.
Thus, loss of thymic vitamin D signaling disrupts normal mTEC differentiation and function and accelerates thymic aging.