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Front. Immunol. | doi: 10.3389/fimmu.2019.00676

Group 3 ILCs: Peacekeepers or troublemakers? What’s your gut telling you?!

 Eirini Pantazi1* and Nick Powell2*
  • 1Kennedy Institute of Rheumatology, University of Oxford, United Kingdom
  • 2Centre for Inflammation Biology and Cancer Immunology, Department of Immunobiology, Faculty of Life Sciences & Medicine, King's College London, United Kingdom

A complex network of interactions exists between the microbiome, the epithelium and immune cells that reside along the walls of the gastrointestinal tract. The intestinal immune system has been assigned with the difficult task of discriminating between commensal, harmless bacteria and invading pathogens that translocate across the epithelial monolayer. Importantly, it is trained to maintain tolerance against commensals, and initiate protective immune responses against pathogens to secure intestinal homeostasis. Breakdown of this fine balance between the host and its intestinal microbiota can lead to intestinal inflammation and subsequently to development of inflammatory bowel disease (IBD). A decade since their discovery, innate lymphoid cells (ILCs) are now recognized as important regulators of intestinal homeostasis. ILC3s have emerged as a critical subset in the gut. They are the most phenotypically diverse ILC population and interact directly with numerous different cell types (haematopoietic and non-haematopoeitic), and well as interfacing with the bacterial flora. In addition to their contribution to intestinal pathogen immunity, they also mitigate against tissue damage occurring following acute injury, by facilitating tissue repair and regeneration, a key function in the maintenance of intestinal homeostasis. However, in chronic inflammation the tables are turned and ILC3s may acquire a pro-inflammatory phenotype in the gut. Chronic ILC activation can lead to persistent inflammation contributing to IBD and/or colorectal cancer. In this review, we discuss current knowledge of group 3 ILCs and their contributions to intestinal homeostasis and disease leading to novel therapeutic targets and clinical approaches that may inform novel treatment strategies for immune-mediated disorders, including IBD.

Keywords: Group 3 Innate lymphoid cells, Symbiosis, intestinal inflammation, IBD, Crohn’s Disease, ulcerative colitis

Received: 31 Aug 2018; Accepted: 12 Mar 2019.

Edited by:

Thomas T. MacDonald, Queen Mary University of London, United Kingdom

Reviewed by:

Mark Travis, University of Manchester, United Kingdom
Rita Carsetti, Bambino Gesù Children Hospital (IRCCS), Italy  

Copyright: © 2019 Pantazi and Powell. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Eirini Pantazi, Kennedy Institute of Rheumatology, University of Oxford, Oxford, OX3 7FY, England, United Kingdom, eirini.pantazi@kennedy.ox.ac.uk
Dr. Nick Powell, Centre for Inflammation Biology and Cancer Immunology, Department of Immunobiology, Faculty of Life Sciences & Medicine, King's College London, London, SE1 1UL, England, United Kingdom, nick.powell@kcl.ac.uk