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Pluripotent stem cell-derived hepatocytes inhibit T cell proliferation in vitro through tryptophan starvation

Research output: Contribution to journalArticlepeer-review

Marco Romano, Raul Elgueta, Daniel McCluskey, Ana Maria Ortega-Prieto, Emilie Stolarczyk, Francesco Dazzi, Baltasar Lucendo-Villarin, Jose Meseguer-Ripolles, James Williams, Giorgia Fanelli, David C Hay, Fiona M Watt, Giovanna Lombardi

Original languageEnglish
Article number24
JournalCells
Volume11
Issue number1
Early online date22 Dec 2021
DOIs
E-pub ahead of print22 Dec 2021
Published1 Jan 2022

Bibliographical note

Funding Information: Acknowledgments: The authors want to acknowledge financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s and St. Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust. The authors acknowledge Research Councils United Kingdom (RCUK) for the support. Funding Information: Funding: This work was funded by funded by the UK Regenerative Medicine Platform (MR/L022699/1 and MR/S020934/1). The Hay lab was funded by an award from the Chief Scientist Office (TCS 16/37). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

King's Authors

Abstract

Regenerative medicine aims to replace damaged tissues by stimulating endogenous tissue repair or by transplanting autologous or allogeneic cells. Due to their capacity to produce unlimited numbers of cells of a given cell type, pluripotent stem cells, whether of embryonic origin or induced via the reprogramming of somatic cells, are of considerable therapeutic interest in the regenerative medicine field. However, regardless of the cell type, host immune responses present a barrier to success. The aim of this study was to investigate in vitro the immunological properties of human pluripotent stem cell (PSC)-derived hepatocyte-like cells (HLCs). These cells expressed MHC class I molecules while they lacked MHC class II and co-stimulatory molecules, such as CD80 and CD86. Following stimulation with IFN-γ, HLCs upregulated CD40, PD-L1 and MHC class I molecules. When co-cultured with allogeneic T cells, HLCs did not induce T cell proliferation; furthermore, when T cells were stimulated via αCD3/CD28 beads, HLCs inhibited their proliferation via IDO1 and tryptophan deprivation. These results demonstrate that PSC-derived HLCs possess immuno-regulatory functions, at least in vitro.

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