Shining a light on Vitamin D
Summer Student Nefisa Marium undertook a project to monitor vitamin D metabolism using human cell culture, rather than using mice. She was supervised by Dr Louisa Jeffery at the University of Birmingham.
Non-communicable diseases including cancer and autoimmune conditions such as rheumatoid arthritis, multiple sclerosis and diabetes are common and increasing in frequency. It is now clear that environmental factors can significantly affect the development and severity of these diseases. Deficiency of vitamin D, the sunlight-acquired vitamin, is one possible risk factor. Vitamin D deficiency is now a global concern, with one-billion people classified vitamin D deficient worldwide.
How does our research help humans?
The vitamin D molecule undergoes a lot of modifications in the body and many of these could have particular effects on the human body. It is therefore important to understand how different human cells handle the different forms of vitamin D. There is much current interest in how deficiency and supplementation of the vitamin influence immune responses.
The aim of this study was to develop a cost-effective in vitro experimental system that could be used to study human immune responsiveness to vitamin D treatment in a standardised way and monitor vitamin D metabolism by human immune cells. This assay would be useful for identifying whether an individual is likely to benefit from vitamin supplementation strategies and whether vitamin D supplementation has had an effect upon human immune cells in the body.
Why did we fund this human-relevant animal-free research?
Most of the research that led to of our current understanding of how vitamin D affects disease has involved the use of mice models of human disease. But due to the distinct differences between the vitamin D system in mice and humans, findings in mice might not truly reflect those in humans. To gain a more accurate idea of how beneficial vitamin D supplementation would be in humans it is necessary to shift this research away from mouse models.
The deficient mouse is not necessarily a good model for vitamin D function. Mice acquire almost all of their vitamin D from their diet, but most humans obtain more than 90% of their vitamin D from the action of sunlight on skin. It is relatively easy to manipulate the vitamin D ‘status’ of mice by simply withholding this part of their food to make them deficient. However, the biological system for obtaining vitamin D from sunlight and diet is very different. Thus, it is impossible to say if mouse diet models are a true representation of variations in vitamin D ’status’ in humans.
Another major limitation in using animal models to assess immune responses to vitamin D is that some key actions of the vitamin are primate-specific, and are therefore not relevant to mice. This is particularly true of the key antibacterial actions of vitamin D that do not appear to occur in mice. It is possible that other aspects of vitamin D immunobiology, including how cells control the levels and different forms, are also better studied away from mouse models. Thus studies of vitamin D and infection need to be carried out in humans.
This study, using human cells and human serum, has established methods by which the variation in human response to vitamin D can be studied across multiple donors. This allows the criteria for its therapeutic use to be defined. The results from this studentship will enable researchers worldwide to gain greater understanding of how vitamin D is truly handled in human health and disease.
The results of this work have been published: L.E. Jeffery et al, Decreased sensitivity to 1,25-dihydroxyvitamin D3 in T cells from the rheumatoid joint, Journal of Autoimmunity (2017). The paper reveals that maintaining sufficient vitamin D levels may help to prevent the onset of inflammatory diseases, like rheumatoid arthritis. You can read an overview of the paper on our blog.
The studentship also helped develop Nefisa as a young researcher. She reflects: “This Animal Free Research UK funded project has made me aware of the importance of non-animal research, particularly the generation of misleading results that can be inapplicable to humans. It has made me aware that there are replacements to animal research, particularly due to innovations in science.
I believe that summer studentships are a great opportunity to spend the summer gaining invaluable research experience and gaining an insight into working in a research environment. This opportunity has definitely helped me in choosing the right career path.”