Areas of interest
The functions of the immune system depend on complex interactions inside the organism, leading to responses to infections that eliminate the pathogen and thus protect from disease.
However, the immune system also has to avoid mounting responses against the body's own healthy cells, otherwise the individual may develop autoimmune diseases such as rheumatoid arthritis, diabetes, and multiple sclerosis.
Our initial studies focused on CD4 T cells, which play a major role in coordinating immune responses and avoiding autoimmunity. CD4 T cells differentiate into specialised subsets characterised by 'signature' cytokines in response to interactions with innate cells such as dendritic cells or macrophages. The complex interplay of cells and soluble mediators that are released upon contact of the organism with a pathogen shapes the type of immune response that develops. Furthermore, such effector T cells display a remarkable degree of plasticity- detected by the use of fate reporter mice- that allows them to widen their scope of effector functions either in pathological settings, or in protective settings.
Dysregulation of inflammatory immune responses can lead to immune pathology and even autoimmunity. We are interested in the critical steps leading to either successful resolution of immune responses or their dysregulation. It is now becoming increasingly clear that so-called innate immune cells, including NKT cells, TCRγδ T cells and innate lymphoid (ILC) cells are of crucial importance in the defence against pathogens and in shaping the adaptive immune response and our focus has widened to include investigations of such cell types.
Inflammatory diseases are influenced by environmental factors which are currently not well defined. We are focusing on a transcription factor, the aryl hydrocarbon receptor (AhR) which transmits environmental signals. AhR has originally been discovered as a receptor for environmental pollutants such as dioxin, but its evolutionary conservation suggests it has important physiological functions beyond this. We initially discovered AhR expression selectively on Th17 cells where it drives the expression of IL-22, but further research has established that AhR expression in barrier organs such as skin, lung and intestine has important beneficial roles in the maintenance of homeostasis.