Regulatory T-cell therapy in Crohn's disease: challenges and advances

Jennifer Clough; Omer Serhan Omer; Scott David Tasker; Graham Michael Lord; Peter M. Irving

doi:10.1136/gutjnl-2019-319850

Regulatory T-cell therapy in Crohn's disease: challenges and advances

Jennifer Clough, Omer Serhan Omer, Scott David Tasker, Graham Michael Lord, Peter M. Irving

Peter Gorer Department of Immunobiology

Research output: Contribution to journal › Review article › peer-review

110 Citations (Scopus)

142 Downloads (Pure)

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.

Original language	English
Pages (from-to)	942-952
Number of pages	11
Journal	Gut
Volume	69
Issue number	5
DOIs	https://doi.org/10.1136/gutjnl-2019-319850
Publication status	Published - 1 May 2020

Keywords

Crohn's disease
T lymphocytes
immunology
immunoregulation
intestinal T cells

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1136/gutjnl-2019-319850

Regulatory T cell therapy_CLOUGH_Accepted19Dec2019_GREEN AAMAccepted author manuscript, 1.17 MB

https://gut.bmj.com/content/gutjnl/early/2020/01/24/gutjnl-2019-319850.full.pdf

Cite this

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title = "Regulatory T-cell therapy in Crohn's disease: challenges and advances",

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.",

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AU - Clough, Jennifer

AU - Omer, Omer Serhan

AU - Tasker, Scott David

AU - Lord, Graham Michael

AU - Irving, Peter M.

PY - 2020/5/1

Y1 - 2020/5/1

N2 - 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.

AB - 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.

KW - Crohn's disease

KW - T lymphocytes

KW - immunology

KW - immunoregulation

KW - intestinal T cells

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U2 - 10.1136/gutjnl-2019-319850

DO - 10.1136/gutjnl-2019-319850

M3 - Review article

SN - 0017-5749

VL - 69

SP - 942

EP - 952

JO - Gut

JF - Gut

IS - 5

ER -

Regulatory T-cell therapy in Crohn's disease: challenges and advances

Abstract

Keywords

UN SDGs

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