Inflammation

Head of Group
Professor Prue Hart

Professor Hart joined the Institute in 2003, following positions at The University of Queensland, Rigshospitalet in Copenhagen, The University of Melbourne and Flinders University.  At the Institute, Professor Hart’s team focuses on the effects of ultraviolet radiation and vitamin D3 on the immune system with their ground-breaking work showing that UV irradiation of mice, with doses equivalent to a short period in the midday sun, can be protective against developing asthmatic symptoms.  The research is now looking at teasing out this protective mechanism with the goal of one day being able to use UV light in safe doses or vitamin D3 to prevent and/or treat asthma.  Professor Hart also has a research programme examining the mechanisms by which interleukin 4 may limit the activity of the immune cells driving chronic inflammation.  Professor Hart is a NHMRC Principal Research Fellow and an Adjunct Professor at UWA. 

Group overview
Members of the Inflammation Research Group are elucidating the mechanisms by which the UVB wavelengths in sunlight can modulate immune responses, particularly those associated with asthma development.  UV exposure is one of the most important environmental factors affecting man.  We know that UV exposure can initiate skin cancers but it is because of a suppressed immune system that these cancers develop and grow and are not immunologically rejected.  The UV-induced suppression of the immune system is systemic and causes reduced responses to allergens delivered to the airways.  The results have been consistent in two models of respiratory airways disease in mice in which UV irradiation of skin reduces some of the hallmark symptoms of asthma.  We have shown that UV-irradiation of skin causes the induction of regulatory cells which when transferred into new mice can modulate immune responses to respiratory allergens.  Extensive studies are ongoing in an attempt to identify and characterise these cells, track them and determine their mode of action.  Studies are also focussing on the immunological potency of vitamin D that is formed in UV-irradiated skin.  As a model we paint the active vitamin D on skin and investigate the immunological consequences.  We have been focussing on CD4+CD25+ cells in the draining lymph nodes.  They have increased activity and gene arrays and functional studies suggest that this is by increased production of interleukin-2.  In other studies we are investigating the effect of UV irradiation of skin on cells in the bone marrow.   Our studies suggest that if we deliver sufficient UV rays to the shaved skin of mice to cause some inflammation (similar to a sunburn), the bone marrow is stimulated to produce altered cells which in turn would be attracted back to the inflamed skin site.  However, as a homeostatic or compensatory response, these cells have reduced immune potential.   

Members of the Inflammation Research Group also study the mechanisms by which anti-inflammatory cytokines can regulate the production of inflammatory mediators by human macrophages and other cells of the monocyte lineage.  We have previously identified new molecules rapidly produced in human monocytes exposed to the anti-inflammatory cytokine, interleukin-4.   In 2008, the regulatory function of suppressor of cytokine signalling-1 (SOCS-1), a molecule rapidly induced by interleukin-4 and lipopolysaccharide and perhaps representing an important mechanism of control by interleukin-4, has been studied.   Monocytes and macrophages were infected with a SOCS-1-encoding virus and the inflammatory mediator production by these infected cells examined.  Studies to examine the anti-inflammatory properties of SOCS-1 and other similar proteins are continuing in human blood monocytes.

Contact
Professor Prue Hart, Head of Group
Email - prueh@ichr.uwa.edu.au
Phone - +61 8 9489 7777
Fax - +61 8 9489 7700