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UKRI Future Leaders Fellow
Research area
Liver immunology; T cell biology; stromal cell interaction.
Research programme
Research summary
The liver - our largest internal organ - acts as a central hub for many physiological processes. Immune responses within the liver are tightly controlled to prevent unnecessary organ damage. Although the liver has an unrivalled ability to regenerate when injured, persistent injury or inflammation can lead to the build-up of scar tissue as it attempts to repair. The build-up of such scar tissue (largely made up of extracellular matrix proteins) can results in liver dysfunction and the development of fibrosis/cirrhosis.
The liver is home to a number of 'residents', that provide specialised immune-surveillance and protection. A population of long-lived, tissue-resident T cells equipped with the necessary armoury and can adapt phenotypically and functionally depending on cues from their microenvironment.
The liver also has a unique population of stromal cells, that when exposed to chronic injury become the master regulators of fibrosis. It is these overactivated stromal cells that differentiate into myofibroblasts that then produce excessive amounts of extracellular matrix proteins, causing the liver to increase in stiffness and functionality to ultimately deteriorate.
The Pallett lab is therefore interested in understanding the role for tissue-resident T cells in the setting of fibrosis and the bi-directional cellular crosstalk between T cells and the local stroma/extracellular matrix. In particular, the Pallett Lab is focussing on how these ‘local intrahepatic cells’ interact in both the healthy and diseased human liver, to inform the development of improved treatments for patients.
Publications
- Selected publications
- Burton AR, Pallett LJ. IL-2 leaves its mark in cirrhosis. J Hepatol. 2021;74(3):505-507
- Pallett LJ, Burton AR, Amin OE, Rodriguez-Tajes S, Patel AA, Zakeri N, Jeffery-Smith A, Swadling L, Schmidt NM, Baiges A, Gander A, Yu D, Nasralla D, Froghi F, Iype S, Davidson BR, Thorburn D, Yona S, Forns X, Maini MK. Longevity and replenishment of human liver-resident memory T cells and mononuclear phagocytes. J Exp Med. 2020;217(9):e20200050
- Swadling L, Pallett LJ, Maini MK. Liver-resident CD8+ T cells: Learning lessons from the local experts. J Hepatol. 2020;72(6):1049-1051
- Swadling L, Pallett LJ, Diniz MO, Baker JM, Amin OE, Stegmann KA, Burton AR, Schmidt NM, Jeffery-Smith A, Zakeri N, Suveizdyte K, Froghi F, Fusai G, Rosenberg WM, Davidson BR, Schurich A, Simon AK, Maini MK. Human Liver Memory CD8+ T Cells Use Autophagy for Tissue Residence. Cell Rep. 2020;30(3):687-698.e6
- Pallett LJ, Schmidt N, Schurich A. T cell metabolism in chronic viral infection. Clin Exp Immunol. 2019;197(2):143-152
- Burton AR, Pallett LJ, McCoy LE, Suveizdyte K, Amin OE, Swadling L, Alberts E, Davidson BR, Kennedy PT, Gill US, Mauri C, Blair PA, Pelletier N, Maini MK. Circulating and intrahepatic antiviral B cells are defective in hepatitis B. J Clin Invest. 2018;128(10):4588-4603
- Amin OE, Colbeck EJ, Daffis S, Khan S, Ramakrishnan D, Pattabiraman D, Chu R, Micolochick Steuer H, Lehar S, Peiser L, Palazzo A, Frey C, Davies J, Javanbakht H, Rosenberg WMC, Fletcher SP, Maini MK, Pallett LJ. Therapeutic Potential of TLR8 Agonist GS-9688 (Selgantolimod) in Chronic Hepatitis B: Remodeling of Antiviral and Regulatory Mediators. Hepatology. 2021;74(1):55-71
- 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.
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