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

Scott P. Davies, Gary M. Reynolds, Alex L. Wilkinson, Xiaoyan Li, Rebecca Rose, Maanav Leekha, Yuxin S. Liu, Ratnam Gandhi, Emma Buckroyd, Joe Grove, Nicholas M. Barnes, Robin C. May, Stefan G. Hubscher, David H. Adams, Yuehua Huang, Omar Qureshi, Zania Stamataki

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12 Citations (Scopus)
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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.
Original languageEnglish
Pages (from-to)1610-1620.e4
Number of pages16
JournalCell Reports
Volume29
Issue number6
DOIs
Publication statusPublished - 5 Nov 2019

Keywords

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

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