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

Davies, SP; Reynolds, GM; Wilkinson, AL; Li, X; Rose, R; Leekha, M; Liu, YS; ... Stamataki, Z; + view all (2019) Hepatocytes Delete Regulatory T Cells by Enclysis, a CD4⁺ T Cell Engulfment Process. Cell Reports , 29 (6) 1610-1620.e4. 10.1016/j.celrep.2019.09.068. Green open access

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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.

Type: Article
Title: Hepatocytes Delete Regulatory T Cells by Enclysis, a CD4⁺ T Cell Engulfment Process
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2019.09.068
Publisher version: https://doi.org/10.1016/j.celrep.2019.09.068
Language: English
Additional information: © 2019 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: T cells, hepatocytes, enclysis, entosis, efferocytosis, endocytosis, emperipolesis, cell-in-cell structures, liverβ-catenin
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10089062
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