Peripheral blood, Liver and Intestine-specific lymphocytes in Primary Sclerosing Cholangitis and Inflammatory Bowel Disease (360G-Wellcome-200154_Z_15_Z)

The focus of my project is on the relationship between the bowel and the liver in Primary Sclerosing Cholangitis (PSC) and Inflammatory Bowel Disease (IBD). This is based on the fact that there is a high rate of IBD in patients with PSC, and it has previously been identified that there is an aberrant population of CCR9+ alpha4beta+ gut-homing T-cells in the PSC liver. Additionally, GWAS and Immunochip™ studies suggest an immune-mediated pathway in the pathogenesis of PSC. I propose to investigate a novel immunologic pathway that could be highly relevant to the development of gut inflammation and the link between gut and liver inflammation. I will examine the CD4+ lymphocyte subset, namely, those expressing CD161 and/or CCR9. I have identified that there is an enrichment of CD161++ CCR9+ CD4+ T-cells in the bowel of patients with PSC and I will be analysing the frequency, phenotype, function, and transcription of these cells in healthy patients, and patients with PSC, IBD, and other liver diseases. I will be examining this lymphocyte subset not only in peripheral blood, but also in liver and intestine. Understanding more about this lymphocyte subset may potentially identify a therapeutic target for this difficult to treat disease.