- Vitamin D deficiency is a risk factor for developing MS, however, the mechanisms that lead to the increased MS risk are not completely understood.
- MS Australia-supported researchers have investigated how vitamin D affects the immune system in people with untreated MS compared to those without MS.
- The researchers found that people living with MS had a reduced response to vitamin D leading to changes in a biological pathway across multiple immune cell types.
Vitamin D and MS
Vitamin D is a hormone that was initially recognised for its importance in bone health. The main sources of vitamin D are synthesis in the skin through ultraviolet B-induced exposure (sunlight), dietary intake or supplements.
Interestingly, when immune cells are grown in a lab and treated with vitamin D, they appear to clear pathogens more effectively in the early stages of the immune response (innate immune system).
They also appear to help regulate the more specialised part of the immune system that provides targeted and long-lasting protection (adaptive immune system).
Vitamin D deficiency is a risk factor for developing MS, as well as several other autoimmune diseases. However, we still don’t understand what mechanisms lead to the increased MS risk.
Several studies have suggested there is a difference in response to vitamin D in immune cells from people living with MS compared to those without MS.
A potential therapeutic role for vitamin D in MS is still in question, and its role in the development of MS is not completely understood.
Additionally, differences in vitamin D immune responses between people with and without MS, as well as different subsets of immune cells, require further investigation.
What did the researchers do?
The study, led by Dr Wei Yeh from Monash University VIC, investigated how vitamin D affects the immune system in people with untreated MS compared to those without MS by studying the activity of certain genes in immune cells.
The researchers focused on the immune cell subsets CD4+ T cells, CD8+ T cells, monocytes and B cells.
Published in Science Reports, the researchers examined which genes were more or less active depending on the levels of vitamin D in people without MS. They then determined what these genes do and how they might be connected.
Next, they looked at whether these genes behaved differently in people with MS in the presence of different vitamin D levels. By doing this, they hoped to understand how having low levels of vitamin D might increase the risk of developing MS.
What did the researchers find?
The researchers found that the levels of 1079 genes in CD4+ T cells and 1188 genes in CD8+ T cells correlated with vitamin D levels in the blood of people without MS.
They also found 858 genes in monocytes and 731 genes in B cells that were also associated with vitamin D levels in the blood of people without MS.
Interestingly, levels of genes in CD4+ T cells that correlated with vitamin D levels were found more often in areas of the genome linked to MS risk in people without MS. This was not the case for the other immune cell subtypes.
In contrast, fewer groups of genes were associated with vitamin D levels in people with MS, suggesting that individuals with MS may have a weaker response to vitamin D.
Delving deeper, the researchers compared the levels of genes that correlated with vitamin D between people with MS and people without MS to understand what these genes do.
They found that the regulation of a specific immune system signalling pathway, known as TNF-alpha signalling, differed in response to vitamin D between individuals with MS and those without MS across multiple immune cell types.
TNF-alpha is a small protein with a broad range of functions, including inflammation.
Elevated TNF-alpha levels detected in the cerebrospinal fluid (fluid surrounding the brain and spinal cord) in people living with MS have been found to be associated with disease activity.
What is the significance of this research?
The results of this study suggest that abnormal TNF-alpha signalling, either due to vitamin D deficiency or the inability to respond to vitamin D, could play a role in how MS develops.
Further work focusing on vitamin D supplementation and the use of advanced technologies to analyse large biological data will further clarify the effects of vitamin D on people with and without MS. This knowledge will hopefully lead to improved ways to prevent and treat MS.
