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.
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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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