The Gastrointestinal Research Group
Associate Professor, Department of Medicine, Division of GastroenterologyImmunology and Gastrointestinal Research Group
FRCP, Royal College of Physicians of London, UK
CCT, Postgraduate Medical and Training Board, UK
PhD, University of Birmingham, UK
MRCP, Royal College of Physicians of London, UK
Dr Eksteen is associate professor of medicine at the University of Calgary. He is a transplant hepatologist at the Foothills Hospital and is part of the Snyder Institute. His research and clinical interests are focused on chronic inflammatory liver diseases such as Primary Sclerosing Cholangitis (PSC) and the immune processes that underpin them.
Discovering a role for mucosal T cells in Primary Sclerosing Cholangitis(PSC) and Inflammatory Bowel Disease (IBD).
I have pioneered studies into the pathogenesis of Primary sclerosing cholangitis (PSC). PSC is an auto-immune liver disease that occurs as an extra-intestinal manifestation of inflammatory bowel disease (IBD). To explain this link between the gut and the liver, I proposed the existence of an entero-hepatic pathway of lymphocyte trafficking in which lymphocytes activated in the gut migrate to the liver and contribute to liver inflammation. In support of this hypothesis, I was the first to show that ectopic expression of the gut restricted chemokine, CCL25 outside of the gut and the presence mucosal CCR9+ α4β7+ T cells in the PSC liver. To support this hypothesis further, I have shown that mucosal T cells in the liver can only be generated by gut dendritic cells. This has provided a new paradigm to explain extra-intestinal diseases that occur as part of IBD and paved the way for novel treatments in a disease (PSC) for which there is currently none apart from liver transplantation. Eksteen B et al. J Exp Med 2004. Eksteen B et al. J Immunol 2006. Adams DH, Eksteen B. Nat Rev Immunol 2006. Eksteen B et al. Gastroenterology 2009.
Defining that intestinal dendritic cells control gut trafficking of T and B cells by retinoic acid secretion.
In order to define how mucosal homing lymphocytes are generated and adaptive immune responses are targeted to the gut I initiated collaborations with Dr Mora and Prof von Andrian in Harvard and Prof Agace in Sweden and were able to show that expression of gut homing receptors are retinoic acid dependent and only imprinted on T and IgA secreting B cells during activation by specific CD103+ dendritic cells (DC) in the gut. Mora JR, Iwata M, Eksteen B et al. Science 2006. Jaensson E et al. J Exp Med 2008.
Operating grants from the American Liver Foundation(USA), the MRC (UK) and the Bowel Disease Research Foundation (UK). He is part of a $6 million Alberta Innovates grant to examine the genetics, immunology and environmental factors that contribute to IBD and PSC .At present Dr Eksteen also holds a MRC Clinician Scientist Fellowship and affiliation with the MRC Centre for Immune Regulation and the NIHR Biomedical Liver Research Unit at the University of Birmingham, UK. Dr Eksteen has held major research grants from the MRC, Wellcome Trust, CORE charity and the British Liver Foundation.
His work has acknowledged by several awards including the Medical Research Society/Academy of Medical Sciences/RCP Young Investigators Award, Royal College of Physicians in 2006, the Dame Sheila Sherlock Research prize from the British Association for the Study of the Liver (BASL) in 2007 and in 2010 the Sir Francis Avery Jones Research Medal from the British Society of Gastroenterology. He is the 2011 Association of National European and Mediterranean Societies of Gastroenterology (ASNEMGE) rising Star recipient.
Oo YH, Weston CJ, Lalor PF, Curbishley SM, Reynolds GM, Eksteen B, Graham N, Hubscher SG, Withers DR, Walker LSK, Adams DH. Distinct roles for CCR4 and CXCR3 in recruitment and positioning of regulatory T cells in inflamed human liver. J Immunol. 2010 Feb 17
Eksteen B, Mora JR, Haughton EL et al. Gut homing receptors on CD8 T-cells ARE retinoic acid dependent and not maintained by Liver dendritic or stellate cells. Gastroenterology 2009 Jul;137(1):320-9.
Adams DH, Eksteen B. Aberrant homing of mucosal T cells and extra-intestinal manifestations of inflammatory bowel disease. Nat Rev Immunol 2006;6(3):244-251.
Mora JR, Iwata M, Eksteen B et al. Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells. Science 2006;314(5802):1157-1160.
Eksteen B, Grant AJ, Miles A et al. Hepatic endothelial CCL25 mediates the recruitment of CCR9+ gut-homing lymphocytes to the liver in primary sclerosing cholangitis. J Exp Med 2004;200(11):1511-7.
Danielle Reid (PhD)