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It has long been known that vitamin D deficiency is associated with autoimmune diseases such as multiple sclerosis (MS) but the exact mechanism has remained elusive.
With the help of a genetic clue from Multiple Sclerosis studies, researchers from the Institute’s Centre for Immunology and Allergy Research have identified how immune cells are controlled by vitamin D.
Westmead Institute researchers have also found that this control would impact other autoimmune diseases, such as Crohn’s disease and rheumatoid arthritis. The risk genes for all these diseases are regulated by vitamin D in particular immune cells.
According to Professor David Booth who leads the Westmead Institute’s Immunogenetic Research Group, the genetic link indicates how the long-observed increase in the risk of contracting MS among those who live in areas with less sunlight might be mediated.
“It’s long been known that your risk of getting MS depended on where you grew up,” Professor Booth says. “For example, if you grew up in North Queensland, your risk is tenfold lower than if you grew up in Tasmania. And that’s replicated around the world. The closer you are to the equator when you grow up, the less likely you are to get MS. It’s a very big difference.”
The key to their significant discovery was knowing where to look. Previous research has focused on the wrong types of immune cells.
Using genetic discoveries from a worldwide collaboration called the International MS Genetics Consortium – of which the Institute researchers were a part – Professor Booth and his team discovered that three known MS-risk genes which control vitamin D activation are “turned on” in specific cells called myeloid cells.
Myeloid cells are a type of immune cell found in the skin and lymph nodes. Until now, nobody has looked at these cells in relation to MS and vitamin D.
With the help of a powerful technique called ChIP-Seq, which analyses protein interactions with DNA, they found that the genes, including the risk genes, are controlled by vitamin D in the myeloid cells.
“That’s a smoking gun,” says Professor Booth. “It suggests that vitamin D controls tolerance through its gene regulation in these skin and lymph node immune cells. It tells you how vitamin D matters.”
However, before you rush off to take vitamin D pills or sunbake, the research, published in the journal Genes and Immunity last week shows that there are probably more effective ways of using vitamin D as an MS therapy.
“Until now, nobody knew how to benefit from this association of vitamin D and MS,” says Professor Booth. “The simplest idea is just to get vitamin D levels up by taking an oral supplement. But our research shows that this might not be the best approach.”
“By manipulating this genetic process we may be better able to use vitamin D and its many analogues in therapy, and also identify new therapeutic approaches, such as methods to control immune cell activation for cell-mediated therapy.”
The next step for the researchers is to extend their examination to the entire spectrum of myeloid cell types to elicit a broader understanding of how vitamin D provides protection.
“In this study, we looked at three cell types, which were the ends of the spectrum. We will now look at 23 cell types – the entire spectrum – with this same technique. This should lead to a better way to manipulate the immune response.”
Multiple sclerosis (MS) is a condition of the central nervous system, interfering with nerve impulses within the brain, spinal cord and optic nerves. According to MS Australia, MS affects over 23,000 people in Australia, with most people diagnosed between the ages of 20-40.
Expert Reaction
These comments have been collated by the Science Media Centre to provide a variety of expert perspectives on this issue. Feel free to use these quotes in your stories. Views expressed are the personal opinions of the experts named. They do not represent the views of the SMC or any other organisation unless specifically stated.
Associate Professor Craig Sinclair is the Head of Prevention Division at the Cancer Council of Victoria
While this is very interesting research, it’s important that Australians don’t use it as an excuse to deliberately seek more sun and put themselves at risk of skin cancer.
At this time of year when UV levels are high across the country, most Australians get enough vitamin D through just a few minutes of sun while doing day-to-day activities – for instance walking to the car or letterbox. Over 2000 Australians die from skin cancer, so sun protection when UV levels are 3 or above must remain the priority.
While Vitamin D is important to health, experts agree that it’s possible to get enough without putting yourself at risk of skin cancer. Sun protection is not required when UV levels are below 3. Australians living in the southern parts of the country, for instance Victoria, Adelaide and Tasmania, can help maintain their Vitamin D in winter when UV levels are low (below 3) by spending some time outdoors in the middle of the day and doing some physical activity.
“There are some groups who are at higher risk of vitamin D deficiency – they include those who cover their skin for religious or cultural reasons, those with particularly dark skin pigmentation, those who live mainly indoors and those on particular medications or with certain medical conditions. We encourage those at higher risk of vitamin D deficiency to speak to their doctor.
Professor Robyn Lucas is a Professor of Environment Climate and Health and Head of the National Centre for Epidemiology and Population Health at The Australian National University
The results reported today do not suggest that high vitamin D levels can reduce the risk or the severity of these diseases. They provide an interesting insight into the possible pathways whereby vitamin D can affect disease. To our best knowledge, maintaining normal vitamin D levels (above 50nmol/L) is optimal for health and this can be achieved for most people with small amounts of sun exposure to the arms, legs and trunk, as advised by Cancer Council Australia in their recent position statement.
In the paper released today in Genes and Immunity, Australian researchers show that particular white blood cells that are involved in immune function express genes that mediate the activity of vitamin D. These specific white blood cells have not been well-studied in relation to vitamin D and autoimmune diseases previously. The research may help to unravel the immune pathways that lead to autoimmune diseases and new treatments for these diseases. The researchers show that genes that have been previously implicated in a range of autoimmune diseases may be regulated by vitamin D in these immune cells.
There is strong evidence of a latitude gradient for the autoimmune diseases multiple sclerosis and type 1 diabetes. The evidence for the other diseases noted in the paper, inflammatory bowel disease, rheumatoid arthritis and systemic lupus erythematosus is contradictory. It is this latitude gradient that first raised questions of a role for vitamin D deficiency in the risk of multiple sclerosis and type 1 diabetes. People with autoimmune diseases typically have lower vitamin D levels than a healthy population, but whether this is a cause of the disease, or caused by the disease, is unclear. The best evidence that vitamin D deficiency increases the risk of an autoimmune disease is for multiple sclerosis.