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Tipping the balance: inhibitory checkpoints in intestinal homeostasis

Joosse, ME; Nederlof, I; Walker, LSK; Samsom, JN; (2019) Tipping the balance: inhibitory checkpoints in intestinal homeostasis. Mucosal Immunology , 12 pp. 21-35. 10.1038/s41385-018-0113-5. Green open access

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Abstract

The small intestinal and colonic lamina propria are populated with forkhead box P3 (FOXP3)+CD4+ regulatory T cells (Tregs) and interleukin-10-producing T cells that orchestrate intestinal tolerance to harmless microbial and food antigens. Expression of co-inhibitory receptors such as CTLA-4 and PD-1 serve as checkpoints to these cells controlling their T-cell receptor (TCR)-mediated and CD28-mediated activation and modulating the phenotype of neighboring antigen presenting cells. Recent discoveries on the diversity of co-inhibitory receptors and their selective cellular expression has shed new light on their tissue-dependent function. In this review, we provide an overview of the co-inhibitory pathways and checkpoints of Treg and effector T cells and their mechanisms of action in intestinal homeostasis. Better understanding of these inhibitory checkpoints is desired as their blockade harbors clinical potential for the treatment of cancer and their stimulation may offer new opportunities to treat chronic intestinal inflammation such as inflammatory bowel disease.

Type: Article
Title: Tipping the balance: inhibitory checkpoints in intestinal homeostasis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41385-018-0113-5
Publisher version: https://doi.org/10.1038/s41385-018-0113-5
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10066463
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