Anne Cooke is available for consultancy.
We study factors governing the onset of autoimmunity and investigate strategies to restore self tolerance and repair damaged tissue. In terms of factors governing the onset of the autoimmune disease type 1 diabetes we have been particularly interested in the interrelationship between infection, autoimmunity and the genetic predisposition to autoimmune disease. Autoimmune diseases such as Type 1 diabetes are increasing in incidence in the developed world faster than can be acounted for by genetic change. Onset of Type 1 diabetes and most other autoimmune diseases is governed by both genetic and environmental factors. Our study of environmental factors has highlighted a key role for infection in reducing the incidence of Type 1 diabetes. We find that protection from diabetes arises through an interaction between the infectious agent and the innate immune system such that circuits which regulate the autoimmune response are reinforced. These studies are carried out in collaboration with Professor D Dunne (Microbiology and Parasitology) and Dr P Mastroeni at the Vet School.
Many genes influence the development of Type 1 diabetes. While some genes such as those encoding MHC class II molecules play a major role other genes have been more difficult to identify. Dr Jenny Nichols and I have generated NOD ES cells and these will be used to identify and characterise genes involved in diabetes development in NOD mice.
phagocytosis ; co-stimulation ; comparative immunology ; co-stimulatory molecules ; microscopy ; anergy ; regulatory T cells ; natural killer cells ; granzymes/perforin/lysosomal ; scavenger receptors ; differentiation ; cytokine/interleukin/chemokine receptors ; antigen presentation ; endothelial cells ; T cell receptor (TCR) ; cytokines ; memory cells ; NK ; genetics ; helper T cells ; adhesion molecules ; interleukin ; immune regulation ; inflammation ; monocytes ; mast cells ; PCR, microarray ; tolerance ; enzyme assays ; immunohistochemistry ; antigen processing ; Fc receptors ; macrophages ; cytotoxic T cells (CTL) ; T cells ; animal models ; traffic ; gamma delta T cells ; suppression ; pattern recognition receptors ; nitric oxide ; binding assays ; negative/positive selection ; evolution ; circulation ; lectins ; cell surface molecules ; cell culture ; cell development ; chemokines/monokines ; immune complexes ; fluorescence microscopy ; stem cells ; basophils ; FACS ; dendritic cells ; migration
Bending D, Zaccone P, Cooke A. Inflammation and type one diabetes. Int Immunol. 2012 Jun;24(6):339-46.
Bending D, Newland S, Krejcí A, Phillips JM, Bray S, Cooke A. Epigenetic changes at Il12rb2 and Tbx21 in relation to plasticity behavior of Th17 cells. J Immunol. 2011 186:3373-82
Zaccone P and Cooke A. Infectious triggers protect from autoimmunity.Seminars in Immunol. 2011 23:122-9.
Haskins K, Cooke A. CD4 T cells and their antigens in the pathogenesis of autoimmune diabetes. Curr Opin Immunol. 2011 Dec;23(6):739-45.
Lehuen A, Diana J, Zaccone P and Cooke A. Immune cell crosstalk in Type 1 diabetes. Nature Reviews Immunology 2010 10:501-13.
Burton OT, Zaccone P, Phillips JM, De La Peña H, Fehérvári Z, Azuma M, Gibbs S, Stockinger B, Cooke A. Roles for TGF-beta and programmed cell death 1 ligand 1 in regulatory T cell expansion and diabetes suppression by zymosan in nonobese diabetic mice. J Immunol. 2010 185:2754-62.