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Cell Rep. 2019 Nov 5;29(6):1610-1620.e4. doi: 10.1016/j.celrep.2019.09.068.

Hepatocytes Delete Regulatory T Cells by Enclysis, a CD4+ T Cell Engulfment Process.

Author information

1
Institute of Immunology and Immunotherapy, Centre for Liver and Gastrointestinal Research, University of Birmingham, Birmingham, UK.
2
Institute of Immunology and Immunotherapy, Centre for Liver and Gastrointestinal Research, University of Birmingham, Birmingham, UK; NIHR Birmingham Liver Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
3
Institute of Immunology and Immunotherapy, Centre for Liver and Gastrointestinal Research, University of Birmingham, Birmingham, UK; Department of Infectious Diseases and Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
4
Institute of Inflammation and Aging, University of Birmingham, Birmingham, UK.
5
Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK.
6
Neuropharmacology Research Group, Institute of Clinical Sciences, University of Birmingham, Birmingham, UK.
7
Institute of Microbiology and Infection and School of Biosciences, University of Birmingham, Birmingham, UK.
8
Institute of Immunology and Immunotherapy, Centre for Liver and Gastrointestinal Research, University of Birmingham, Birmingham, UK; NIHR Birmingham Liver Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; Department of Cellular Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
9
Department of Infectious Diseases and Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
10
Celentyx Ltd., Birmingham Research Park, Birmingham B15 2SQ, UK; Celentyx Ltd., BioEscalator Innovation Building, Oxford OX3 7FZ, UK.
11
Institute of Immunology and Immunotherapy, Centre for Liver and Gastrointestinal Research, University of Birmingham, Birmingham, UK; NIHR Birmingham Liver Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. Electronic address: z.stamataki@bham.ac.uk.

Abstract

CD4+ T cells play critical roles in directing immunity, both as T helper and as regulatory T (Treg) cells. Here, we demonstrate that hepatocytes can modulate T cell populations through engulfment of live CD4+ lymphocytes. We term this phenomenon enclysis to reflect the specific enclosure of CD4+ T cells in hepatocytes. Enclysis is selective for CD4+ but not CD8+ cells, independent of antigen-specific activation, and occurs in human hepatocytes in vitro, ex vivo, and in vivo. Intercellular adhesion molecule 1 (ICAM-1) facilitates T cell early adhesion and internalization, whereas hepatocytes form membrane lamellipodia or blebs to mediate engulfment. T cell internalization is unaffected by wortmannin and Rho kinase inhibition. Hepatocytes engulf Treg cells more efficiently than non-Treg cells, but Treg cell-containing vesicles preferentially acidify overnight. Thus, enclysis is a biological process with potential effects on immunomodulation and opens a new field for research to fully understand CD4+ T cell dynamics in liver inflammation.

KEYWORDS:

T cells; cell-in-cell structures; efferocytosis; emperipolesis; enclysis; endocytosis; entosis; hepatocytes; liver; β-catenin

PMID:
31693899
DOI:
10.1016/j.celrep.2019.09.068
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