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Recent advances in basic science
Regulatory T-cell therapy in Crohn’s disease: challenges and advances
  1. Jennie N Clough1,2,
  2. Omer S Omer1,3,
  3. Scott Tasker4,
  4. Graham M Lord1,5,
  5. Peter M Irving1,3
  1. 1 School of Immunology and Microbial Sciences, King's College London, London, UK
  2. 2 NIHR Biomedical Research Centre at Guy's and Saint Thomas' NHS Foundation Trust and King's College, London, UK
  3. 3 Department of Gastroenterology, Guy's and Saint Thomas' Hospitals NHS Trust, London, UK
  4. 4 Division of Transplantation Immunology and Mucosal Biology, King's College London, London, UK
  5. 5 Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
  1. Correspondence to Dr Peter M Irving, Department of Gastroenterology, Guy's and Saint Thomas' NHS Foundation Trust, London SE1 9RT, UK; peter.irving{at}kcl.ac.uk

Abstract

The prevalence of IBD is rising in the Western world. Despite an increasing repertoire of therapeutic targets, a significant proportion of patients suffer chronic morbidity. Studies in mice and humans have highlighted the critical role of regulatory T cells in immune homeostasis, with defects in number and suppressive function of regulatory T cells seen in patients with Crohn’s disease. We review the function of regulatory T cells and the pathways by which they exert immune tolerance in the intestinal mucosa. We explore the principles and challenges of manufacturing a cell therapy, and discuss clinical trial evidence to date for their safety and efficacy in human disease, with particular focus on the development of a regulatory T-cell therapy for Crohn’s disease.

  • Crohn's disease
  • immunology
  • immunoregulation
  • intestinal T cells
  • T lymphocytes
https://creativecommons.org/licenses/by/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

https://doi.org/10.1136/gutjnl-2019-319850

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    Footnotes

    • JNC and OSO contributed equally.

    • Contributors JNC and OSO performed a systematic literature search. JNC, OSO and ST wrote the manuscript and created the table and figures. GML and PMI reviewed the article and contributed to critical revisions of the manuscript. All authors have approved the final version of this article.

    • Disclaimer The views expressed are those of the author(s) and not necessarily those of the National Health Service, the NIHR or the Department of Health.

    • Competing interests PMI is the Chief Investigator and GML is the Chief Scientific Investigator on the Medical Research Council-funded TRIBUTE trial of Treg immunotherapy in CD (ClinicalTrials.gov NCT03185000).

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.