Professor Simon Arthur

The body's immune system is essential for defence against infection and wound healing. However excessive, or inappropriate, activation of the immune system results in unwanted damage to healthy tissue. Infection or injury is detected by immune cells, which then trigger a complex inflammatory reaction designed to clear the pathogen and/or promote tissue repair. Normally this is then followed by a resolution phase during which inflammation decreases and the immune system is deactivated. Excessive inflammation, however, can cause tissue damage or cytokine storms. In severe cases, this can result in septic shock, a condition that still has limited treatment options and high mortality. A failure of resolution results in chronic inflammation, a condition that underlies the pathology of autoimmune and auto-inflammatory conditions. These diseases, which include rheumatoid arthritis, psoriasis, lupus and vasculitis, represent a major health problem, and together can affect 3-4% of the population in Western society. Autoimmune disorders are often serious and can lead to significant disability and in some cases mortality. While modern drug treatments can be effective in providing relief from these conditions, they do not provide a cure and can themselves result in significant adverse side effects. Thus more research is needed to provide a full understanding of the causes and pathology of these conditions to enable improved therapies to be developed. Inflammation is a complex multistage process involving multiple cell types from both the innate and adaptive immune systems and is tightly coordinated by a range of pro-inflammatory cytokines and chemokines. Further control is also achieved via the induction of anti-inflammatory cytokines that act to keep inflammation within acceptable limits and to promote the resolution of inflammation.

We are primarily interested in the roles that cells of the innate immune system play in coordinating inflammation and how they contribute to the activation of adaptive immunity via the production of cytokines. Innate immune cells are able to recognize specific components of pathogens – referred to as pathogen-associated molecular patterns or PAMPs. Several groups of receptors for PAMPs have been described, including Toll-like receptors, C-type lectins and NOD-like proteins. These receptors trigger the activation of several intracellular signalling pathways, including the mitogen-activated protein kinase (MAPK), NFkappaB and TBK1/IRF systems leading to the transcription and production of both pro-and anti-inflammatory cytokines. Our main focus is to understand the roles these intracellular signalling cascades play in both the initial inflammatory response and in the ability of innate immune cells, particularly macrophages and dendritic cells, to activate the adaptive immune system. Finally, we are interested in the ways in which intracellular signalling in innate immune cells controls the induction of anti-inflammatory and pro-resolution factors in order to deactivate the immune system.

BS31006 - Genetics

BS32006 - Cell Signalling

BS32009 - Immunology

BS42006 - Advanced Immunology

BS42013 - Advanced Cell Signalling