Hepatocytes delete regulatory T cells by enclysis, a CD4+ T cell engulfment process

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Hepatocytes delete regulatory T cells by enclysis, a CD4+ T cell engulfment process. / Davies, Scott P.; Reynolds, Gary M.; Wilkinson, Alex L.; Li, Xiaoyan; Rose, Rebecca; Leekha, Maanav; Liu, Yuxin S.; Gandhi, Ratnam; Buckroyd, Emma; Grove, Joe; Barnes, Nicholas M.; May, Robin C.; Hubscher, Stefan G.; Adams, David H.; Huang, Yuehua; Qureshi, Omar; Stamataki, Zania.

In: Cell Reports, Vol. 29, No. 6, 05.11.2019, p. 1610-1620.e4.

Research output: Contribution to journalArticlepeer-review

Harvard

Davies, SP, Reynolds, GM, Wilkinson, AL, Li, X, Rose, R, Leekha, M, Liu, YS, Gandhi, R, Buckroyd, E, Grove, J, Barnes, NM, May, RC, Hubscher, SG, Adams, DH, Huang, Y, Qureshi, O & Stamataki, Z 2019, 'Hepatocytes delete regulatory T cells by enclysis, a CD4+ T cell engulfment process', Cell Reports, vol. 29, no. 6, pp. 1610-1620.e4. https://doi.org/10.1016/j.celrep.2019.09.068

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Author

Davies, Scott P. ; Reynolds, Gary M. ; Wilkinson, Alex L. ; Li, Xiaoyan ; Rose, Rebecca ; Leekha, Maanav ; Liu, Yuxin S. ; Gandhi, Ratnam ; Buckroyd, Emma ; Grove, Joe ; Barnes, Nicholas M. ; May, Robin C. ; Hubscher, Stefan G. ; Adams, David H. ; Huang, Yuehua ; Qureshi, Omar ; Stamataki, Zania. / Hepatocytes delete regulatory T cells by enclysis, a CD4+ T cell engulfment process. In: Cell Reports. 2019 ; Vol. 29, No. 6. pp. 1610-1620.e4.

Bibtex

@article{276e5c1f1ff04617b67179a87a5ae19f,
title = "Hepatocytes delete regulatory T cells by enclysis, a CD4+ T cell engulfment process",
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, hepatocytes, enclysis, entosis, efferocytosis, endocytosis, emperipolesis, cell-in-cell structures, liver, β-catenin",
author = "Davies, {Scott P.} and Reynolds, {Gary M.} and Wilkinson, {Alex L.} and Xiaoyan Li and Rebecca Rose and Maanav Leekha and Liu, {Yuxin S.} and Ratnam Gandhi and Emma Buckroyd and Joe Grove and Barnes, {Nicholas M.} and May, {Robin C.} and Hubscher, {Stefan G.} and Adams, {David H.} and Yuehua Huang and Omar Qureshi and Zania Stamataki",
year = "2019",
month = nov,
day = "5",
doi = "10.1016/j.celrep.2019.09.068",
language = "English",
volume = "29",
pages = "1610--1620.e4",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Elsevier",
number = "6",

}

RIS

TY - JOUR

T1 - Hepatocytes delete regulatory T cells by enclysis, a CD4+ T cell engulfment process

AU - Davies, Scott P.

AU - Reynolds, Gary M.

AU - Wilkinson, Alex L.

AU - Li, Xiaoyan

AU - Rose, Rebecca

AU - Leekha, Maanav

AU - Liu, Yuxin S.

AU - Gandhi, Ratnam

AU - Buckroyd, Emma

AU - Grove, Joe

AU - Barnes, Nicholas M.

AU - May, Robin C.

AU - Hubscher, Stefan G.

AU - Adams, David H.

AU - Huang, Yuehua

AU - Qureshi, Omar

AU - Stamataki, Zania

PY - 2019/11/5

Y1 - 2019/11/5

N2 - 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.

AB - 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.

KW - T cells

KW - hepatocytes

KW - enclysis

KW - entosis

KW - efferocytosis

KW - endocytosis

KW - emperipolesis

KW - cell-in-cell structures

KW - liver

KW - β-catenin

U2 - 10.1016/j.celrep.2019.09.068

DO - 10.1016/j.celrep.2019.09.068

M3 - Article

C2 - 31693899

VL - 29

SP - 1610-1620.e4

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 6

ER -