Tissue Immunity

Our work

At the IIT, we are fortunate to receive surplus samples from various organs from the surgeons working at the adjacent Royal Free Hospital. This allows us to study immune responses directly isolated from the site of disease, rather than just the fraction that is circulating in the blood.

Many immune cells are compartmentalised within tissues, with specialised adaptations to these sites, and these cannot be sampled from blood. Analysing tissue immunity therefore provides vital insights into the responses providing frontline defence and/or driving damage. 

Our work aims to use this research to develop biomarkers and immunotherapies targeted to the disease site.

Liver-resident T cells: adaptation & function

We are investigating how the landscape of the liver influences the phenotypic, metabolic and functional profile of liver-infiltrating and liver-resident T cells using primary human tissue samples. We are also examining cellular interactions occurring within the liver that further shape the effector function of T cells in the context of chronic liver diseases.

Lead Investigators

• Dr Laura Pallett (Institute of Immunity & Transplantation, UCL)
• Professor Mala Maini (Institute of Immunity & Transplantation, UCL)

Cellular-cross talk in liver fibrosis

We are examining the interplay between liver-resident T cells and the stromal cell niche in the human liver. We are specifically interested in understanding how liver-resident T cells interact and communicate with hepatic stellate cells to cross-regulate cell distribution, survival, function and fibrogenic potential to exacerbate (or limit) the development of liver fibrosis.

Lead investigator

• Dr Laura Pallett (Institute of Immunity & Transplantation, UCL)

Interplay between T cells, myeloid cells and microbial products in liver disease

We have defined a novel mechanism of myeloid instruction of tissue T cells and are studying how this calibrates liver-resident T cell homeostatic, TCR and LPS-dependent effector function in different disease settings and could be harnessed in immunotherapy.

Lead investigators

• Dr Laura Pallett (Institute of Immunity & Transplantation, UCL)
• Professor Mala Maini (Institute of Immunity & Transplantation, UCL)

Our experts

Selected publications

1. Pallett LJ, Swadling L, Diniz M ... Maini MK (2023). Tissue CD14+CD8+ T cells reprogrammed by myeloid cells and modulated by LPS. Nature. 2023 Feb; 614(7947): 334-342.
2. Wiggins BG, Pallett LJ, Li X ... Maini MK, Stamataki Z (2022). The human liver microenvironment shapes the homing and function of CD4+ T-cell populations. Gut. 2022 Jul;71(7): 1399-1411.
3. Amin OE, Colbeck EJ, Daffis S ... Maini MK, Pallett LJ (2021). Therapeutic Potential of TLR8 Agonist GS-9688 (Selgantolimod) in Chronic Hepatitis B: Remodeling of Antiviral and Regulatory Mediators. Hepatology. 2021 Jul;74(1):55-71.
4. Pallett LJ, Burton AR, Amin OE ... Maini MK (2020). Longevity and replenishment of human liver-resident memory T cells and mononuclear phagocytes. J Exp Med. 2020 Sep 7;217(9): e20200050.
5. Swadling L, Pallett LJ, Diniz MO, Baker JM ... Maini MK (2020). Human Liver Memory CD8+ T Cells Use Autophagy for Tissue Residence. Cell Rep. 2020 Jan 21;30(3): 687-698.e6.
6. Gill US, Pallett LJ, Thomas N, Burton AR, Patel AA, Yona S, Kennedy PTF, Maini MK (2019). Fine needle aspirates comprehensively sample intrahepatic immunity. Gut. 2019 Aug;68(8): 1493-1503.
7. Pallett LJ, Davies J, Colbeck EJ ... Maini MK (2017). IL-2high tissue-resident T cells in the human liver: Sentinels for hepatotropic infection. J Exp Med. 2017 Jun 5;214(6): 1567-1580.

Adapting to life in the liver: An immune cell perspective

We are continually influenced by our location, environment, the people we meet, and even how hungry we are at any moment. Immune cells are no different. For World Liver Day, Dr Laura Pallett discusses how the identity and function of immune cells is influenced by such factors.