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

Davies, S. P. et al. (2019) Hepatocytes delete regulatory T cells by enclysis, a CD4+ T cell engulfment process. Cell Reports, 29(6), 1610-1620.e4. (doi: 10.1016/j.celrep.2019.09.068) (PMID:31693899) (PMCID:PMC7057271)

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.

• Item Type: Articles
• Additional Information: S.P.D. was funded by a PhD studentship from the Medical Research Council (MRC) Centre for Immune Regulation. X.L. was funded by a Guangzhou Municipal Government (GMG) award (2016201604030021 to Y.H. and Z.S.). A.L.W. was funded by a Wellcome Trust PhD studentship in Mechanisms of Inflammatory Diseases. Y.S.L. was funded by an MRC Confidence in Concept Award (to Z.S.). This work was initiated thanks to support from a small seed award by the Wellcome Trust Institutional Support Fund (to Z.S.). Z.S. has subsequently received funding from the MRC, Wellcome Trust, GMG, The Birmingham Children’s Hospital Research Foundation, and a Royal Society Dorothy Hodgkin fellowship. J.G. is the recipient of a Sir Henry Dale Fellowship from the Wellcome Trust and the Royal Society (107653/Z/15/Z). R.C.M. is supported by the BBSRC, an ERC consolidator award (MitoFun), and a Wolfson Research Merit Award from the Royal Society.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Grove, Dr Joe

Creator Roles

Grove, J.: Investigation

• Authors: Davies, S. P., Reynolds, G. M., Wilkinson, A. L., Li, X., Rose, R., Leekha, M., Liu, Y. S., Gandhi, R., Buckroyd, E., Grove, J., Barnes, N. M., May, R. C., Hubscher, S. G., Adams, D. H., Huang, Y., Qureshi, O., and Stamataki, Z.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Cell Reports
• Publisher: Elsevier (Cell Press)
• ISSN: 2211-1247
• ISSN (Online): 2211-1247
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in Cell Reports 29(6): 1610-1620.e4
• Publisher Policy: Reproduced under a Creative Commons License