Innate Immunity
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Innate immune factors play a critical role in initiating and shaping adaptive immune responses and this is as true for the immune response against autoantigens and transplanted organs as it is for responses against microbial antigens. Research in this section encompasses a diverse set of projects, united by the underlying theme of investigating the importance of innate factors in transplantation, autoimmune renal disease and urological malignancies. The ambition of all the research in this area is to translate this knowledge into new and innovative therapies for clinical application.
The Innate Immunity Section includes research groups working on the following research areas:
- Complement Biology (Professor Steven Sacks, Dr Claudia Kemper, Dr Wuding Zhou)
- Cytotopic Therapeutics (Dr Richard Smith)
- Transplant Inflammation and Repair (Professor Anthony Dorling)
- Vasculitis Laboratory (Dr Mike Robson)
- Experimental Urology (Professor Prokar Dasgupta)
- HLA Laboratory (Dr Robert Vaughan)rn
My research focuses on a novel crosstalk between the complement system, specifically the complement protein CD46, and T cell responses as CD46 signaling induces the development of IL-10-secreting adaptive regulatory T cells (Tregs).
We propose that understanding the underlying mechanisms that shape this novel important interplay between the complement system and T cells would significantly advance our ability to develop more effective immunotherapies to control T cell-mediated disease conditions. Thus, I intend to build a research program aimed at elucidating the role of complement-induced Tregs in normal immune homeostasis and states of chronic inflammation such as autoimmunity or pathogen persistence.
Glomerulonephritis is a common cause of irreversible renal failure leading to the need for dialysis and transplantation. We aim to discover the fundamental causes of these diseases, in addition to the mechanisms that mediate renal inflammation. Our basic research program has used experimental models of glomerulonephritis to explore these mechanisms. In recent years we have dissected the role of the innate immune system and in particular how Toll-like receptors interact with the adaptive immune system and lead to tissue damage. We have also explored the role of specific IgG subclasses and Fc receptors in glomerular inflammation.
We are currently developing a specific interest in one form of glomerulonephritis, namely anti-neutrophil cytoplasmic antibody associated vasculitis (AAV). The figure below shows a glomerulus that has undergone fibrinoid necrosis and crescent formation, as would be seen in AAV. We are pursuing research based both on experimental models of AAV and on patient samples. Myeloperoxidase (MPO) is one of the major autoantigens in AAV and a model of AAV based on the knockout mouse has been published by others. We are using both this model and other novel systems to dissect both the mechanisms of capillary injury and the origin of autoimmunity in AAV. We are also collecting blood samples from newly presenting patients with AAV in order to examine how their white blood cells differ from controls, and to develop new markers of disease activity.
