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 and Stamataki, Zania (2019) Hepatocytes Delete Regulatory T Cells by Enclysis, a CD4 T Cell Engulfment Process. Cell reports, 29 (6). 1610-1620.e4. ISSN 2211-1247.

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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: Article
Subjects: WI Digestive system. Gastroenterology
Divisions: Clinical Support > Pathology
Emergency Services > Renal
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Depositing User: Mrs Yolande Brookes
Date Deposited: 08 Nov 2019 13:43
Last Modified: 08 Nov 2019 13:43
URI: http://www.repository.uhblibrary.co.uk/id/eprint/2561

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