Inflammation

Realisation of the benefits of UV radiation exposure have become more and more important as trials of vitamin D supplementation for conditions for which inverse associations of vitamin D levels and disease incidence or severity have been reported, continue to fail and give less than hoped for benefits. We know that low serum vitamin D levels are a measure of inadequate recent sun exposure. In turn, vitamin D deficiency is a biomarker of low sun exposure and is not causal in mediating, or contributing to, many non-skeletal human diseases.  Instead, a lack of other molecules produced in UV-irradiated skin may be responsible.

The Inflammation Team is investigating the mechanisms or pathways of UV induced immunoregulation, as well as translation of agonists or antagonists able to replicate or regulate, respectively, these pathways for control of human immune conditions.

Our team leads the world-first trial to give UVB phototherapy to patients with an early form of multiple sclerosis called Clinically Isolated Syndrome.

This trial is teaching us much about the effects of UVB light on changes to the immune cells available to us from blood, and we are attempting to correlate these with clinical signs of MS development.  This trial will inform the design of future trials to modulate autoimmune conditions in children and adults.  The clinical trial complements consistent reports of latitudinal gradients for most autoimmune diseases, and our solid ongoing studies in preclinical models of mechanisms of UV control of biological systems.

Our studies have suggested that the effects of UV radiation exposure may be long lasting because of its ability to epigenetically alter myeloid progenitor cells in the bone marrow, such that fully differentiated daughter cells have altered functional properties.

The preclinical and clinical studies continue to support each other with each contributing to ongoing studies of the phenotype and function of blood cells biobanked from the participants in our phototherapy trial.

Our preclinical models of UV-irradiated skin will continue to support discovery projects of biologically important molecules produced in response to different wavelengths of light.

We have identified molecules (other than vitamin D) produced in UV-irradiated skin that could provide novel new approaches to limit chronic graft-versus-host disease in patients that have received bone marrow transplants.

Our Inflammation team understands that Australians are confused about how much sun exposure they should receive.

With greater knowledge of benefits and harms, we can provide evidence-based guidelines and help determine the role of sun to the health of Australians.

Team Highlights

• Successful recruitment of 20 participants into the human PhoCIS trial.
• Successful publication in 2017-18 of 3 reports on the immunoregulatory properties of UV irradiation of the skin of mice on myeloid progenitor cells in the bone marrow (published in J Immunol, Amer J Pathol and Exp Hemataol)
• Publication in 2017 of a review in Clinical and Experimental Immunology (Journal of the British Society for Immunology) that was rated one of the 5 publications with highest citation rates in 2017.
• Publication in April 2018 of the primary outcomes (MRI changes) of the PhoCIS trial (MS Journal: Experimental, Translational, Clinical. 4(2):2055217318773112.
• Publication in July 2018 of two studies of cells and sera from participants in the PhoCIS trial (published in Frontiers Immunology, and Clin Transl Immunol).
• Successful co-ordination and publishing of an invited review to PHH in Annual Reviews Pathology, titled Exposure to Ultraviolet Radiation in Modulation of Human Diseases.
• Successful publication by PhD student, Dr Simon Ghaly, of publications in Scientific Reports and Nutrients of changes to the faecal microbiome of UV-irradiated mice and mice given different vitamin D diets and the relevance of these changes to a their pathology in a model of inflammatory bowel disease.