Professor of Transplant Immunology
Dissecting the immune correlates of viral persistence and liver damage, in order to allow the development of novel immunotherapeutic strategies for hepatitis B virus (HBV).
As well as being of great medical importance in its own right, HBV provides a useful model to provide insights into liver immunology, which has relevance for other hepatotropic infections and malignancies, liver transplantation and autoimmunity.
We are defining specialised cell types and pathways that maintain the uniquely tolerant immunological environment in the liver. Defining these mechanisms is critical to understanding how highly prevalent human pathogens like HBV can persist in this niche. Much of our work takes advantage of our strong clinical links to obtain blood samples from well-characterised patient cohorts and healthy or malignant human liver tissue to study immune responses at the site of disease. We focus on understanding local cell-cell cross-talk and unique influences of the hepatic microenvironment, including metabolic regulation of immunity. We have recently defined populations of liver-resident T cells and NK cells and are investigating how to harness these for immunotherapy.
We are interested in how hepatic immune responses can either mediate protective effects or can cause liver damage leading to the complications of liver cirrhosis and hepatocellular carcinoma (HCC) that still kill an estimated 700,000 people a year with chronic HBV infection. Existing therapies are rarely able to cure HBV or complications like HCC so our goal is to inform the development of tailored boosting of protective antiviral and anti-tumour immunity. We collaborate internationally with academics and industry to contribute to this exciting and fast-moving field of applied research.
- Selected publications
- Pallett LJ, Gill US, Quaglia A, Sinclair LV, Jover-Cobos M, Schurich A, Singh KP, Thomas N, Das A, et al…Maini MK. Metabolic regulation of hepatitis B immunopathology by myeloid-derived suppressor cells. Nat Med. 2015;21(6):591-600
- Stegmann KA, Robertson F, Hansi N, Gill U, Pallant C, Christophides T, Pallett LJ, Peppa D, Dunn C, et al…Maini MK. CXCR6 marks a novel subset of T-betloEomeshi natural killer cells residing in human liver. Sci Rep. 2016;6:26157
- Schurich A, Pallett LJ, Jajbhay D, Wijngaarden J, Otano I, Gill US, Hansi N, Kennedy PT, Nastouli E, Gilson R, Frezza C, Henson SM, Maini MK. Distinct metabolic requirements of exhausted and functional virus-specific CD8 T cells in the same host. Cell Rep. 2016;16(5):1243-52
- Gill US, Peppa D, Micco L, Singh HD, Carey I, Foster GR, Maini MK*, Kennedy PT*. *Joint senior & corresponding authors. Interferon alpha induces sustained changes in NK cell responsiveness to hepatitis B viral load suppression in vivo. PLoS Pathog. 2016;12(8):e1005788
- Huang WC, Easom NJ, Tang XZ, Gill US, Singh H, Robertson F, Chang C, Trowsdale J, Davidson BR, Rosenberg WM, Fusai G, Toubert A, Kennedy PT, Peppa D, Maini MK. T Cells Infiltrating Diseased Liver Express Ligands for the NKG2D Stress Surveillance System. J Immunol. 2017;198(3):1172-1182
- Maini MK, Bertoletti A. HBV in 2016: Global and immunotherapeutic insights into hepatitis B. Nat Rev Gastroenterol Hepatol. 2017;14(2):71-72
- Pallett LJ, Davies J, Colbeck EJ, Robertson F, Hansi N, Easom NJW, Burton AR, Stegmann KA, Schurich A, Swadling L, Gill US, Male V, Luong T, Gander A, Davidson BR, Kennedy PTF, Maini MK. IL-2high tissue-resident T cells in the human liver: Sentinels for hepatotropic infection. J Exp Med. 2017;214(6):1567-1580
- Singh HD, Otano I, Rombouts K, Singh KP, Peppa D, Gill US, Böttcher K, Kennedy PTF, Oben J, Pinzani M, Walczak H, Fusai G, Rosenberg WMC, Maini MK. TRAIL regulatory receptors constrain human hepatic stellate cell apoptosis. Sci Rep. 2017;7(1):5514
- Gill US, Pallett LJ, Kennedy PTF, Maini MK. Liver sampling: a window into HBV pathogenesis on the path to functional cure. Gut. 2018;67(4):767-775
- Maini MK, Pallett LJ. Defective T cell immunity in HBV: why therapeutic vaccination needs a helping hand. Lancet Gastro Hepatology. 2018;3:192-202. In press.
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