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

Research output: Contribution to journalArticle

Authors

  • Gary M. Reynolds
  • Alex L. Wilkinson
  • Xiaoyan Li
  • Rebecca Rose
  • Maanav Leekha
  • Yuxin S. Liu
  • Ratnam Gandhi
  • Emma Buckroyd
  • Joe Grove
  • Yuehua Huang
  • Omar Qureshi
  • Zania Stamataki

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.

Details

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

Keywords

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