T-Bet Controls Cellularity of Intestinal Group 3 Innate Lymphoid Cells

Innate lymphoid cells (ILC) play a significant immunological role at mucosal surfaces such as the intestine. T-bet-expressing group 1 innate lymphoid cells (ILC1) are believed to play a substantial role in inflammatory bowel disease (IBD). However, a role of T-bet-negative ILC3 in driving colitis ha...

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Main Authors: Jan-Hendrik Schroeder, Katrin Meissl, Dominika Hromadová, Jonathan W. Lo, Joana F. Neves, Jane K. Howard, Helena Helmby, Nick Powell, Birgit Strobl, Graham M. Lord
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-02-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2020.623324/full
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author Jan-Hendrik Schroeder
Katrin Meissl
Dominika Hromadová
Jonathan W. Lo
Jonathan W. Lo
Joana F. Neves
Jane K. Howard
Helena Helmby
Nick Powell
Birgit Strobl
Graham M. Lord
Graham M. Lord
author_facet Jan-Hendrik Schroeder
Katrin Meissl
Dominika Hromadová
Jonathan W. Lo
Jonathan W. Lo
Joana F. Neves
Jane K. Howard
Helena Helmby
Nick Powell
Birgit Strobl
Graham M. Lord
Graham M. Lord
author_sort Jan-Hendrik Schroeder
collection DOAJ
description Innate lymphoid cells (ILC) play a significant immunological role at mucosal surfaces such as the intestine. T-bet-expressing group 1 innate lymphoid cells (ILC1) are believed to play a substantial role in inflammatory bowel disease (IBD). However, a role of T-bet-negative ILC3 in driving colitis has also been suggested in mouse models questioning T-bet as a critical factor for IBD. We report here that T-bet deficient mice had a greater cellularity of NKp46-negative ILC3 correlating with enhanced expression of RORγt and IL-7R, but independent of signaling through STAT1 or STAT4. We observed enhanced neutrophilia in the colonic lamina propria (cLP) of these animals, however, we did not detect a greater risk of T-bet-deficient mice to develop spontaneous colitis. Furthermore, by utilizing an in vivo fate-mapping approach, we identified a population of T-bet-positive precursors in NKp46-negative ILC3s. These data suggest that T-bet controls ILC3 cellularity, but does do not drive a pathogenic role of ILC3 in mice with a conventional specific pathogen-free microbiota.
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spelling doaj.art-ba9f9bb4005040f781058400f748fa392022-12-21T20:19:45ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-02-011110.3389/fimmu.2020.623324623324T-Bet Controls Cellularity of Intestinal Group 3 Innate Lymphoid CellsJan-Hendrik Schroeder0Katrin Meissl1Dominika Hromadová2Jonathan W. Lo3Jonathan W. Lo4Joana F. Neves5Jane K. Howard6Helena Helmby7Nick Powell8Birgit Strobl9Graham M. Lord10Graham M. Lord11School of Immunology and Microbial Sciences, King’s College London, London, United KingdomInstitute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, AustriaInstitute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, AustriaSchool of Immunology and Microbial Sciences, King’s College London, London, United KingdomDivision of Digestive Diseases, Faculty of Medicine, Imperial College London, London, United KingdomCentre for Host-Microbiome Interactions, King’s College London, London, United KingdomDepartment of Diabetes, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King’s College, London, United KingdomDepartment of Infection Biology, London School of Hygiene and Tropical Medicine, London, United KingdomDivision of Digestive Diseases, Faculty of Medicine, Imperial College London, London, United KingdomInstitute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, AustriaSchool of Immunology and Microbial Sciences, King’s College London, London, United KingdomFaculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomInnate lymphoid cells (ILC) play a significant immunological role at mucosal surfaces such as the intestine. T-bet-expressing group 1 innate lymphoid cells (ILC1) are believed to play a substantial role in inflammatory bowel disease (IBD). However, a role of T-bet-negative ILC3 in driving colitis has also been suggested in mouse models questioning T-bet as a critical factor for IBD. We report here that T-bet deficient mice had a greater cellularity of NKp46-negative ILC3 correlating with enhanced expression of RORγt and IL-7R, but independent of signaling through STAT1 or STAT4. We observed enhanced neutrophilia in the colonic lamina propria (cLP) of these animals, however, we did not detect a greater risk of T-bet-deficient mice to develop spontaneous colitis. Furthermore, by utilizing an in vivo fate-mapping approach, we identified a population of T-bet-positive precursors in NKp46-negative ILC3s. These data suggest that T-bet controls ILC3 cellularity, but does do not drive a pathogenic role of ILC3 in mice with a conventional specific pathogen-free microbiota.https://www.frontiersin.org/articles/10.3389/fimmu.2020.623324/fullT-betinnate lymphoid cellsILCsintestinal inflammationmucosal homeostasis
spellingShingle Jan-Hendrik Schroeder
Katrin Meissl
Dominika Hromadová
Jonathan W. Lo
Jonathan W. Lo
Joana F. Neves
Jane K. Howard
Helena Helmby
Nick Powell
Birgit Strobl
Graham M. Lord
Graham M. Lord
T-Bet Controls Cellularity of Intestinal Group 3 Innate Lymphoid Cells
Frontiers in Immunology
T-bet
innate lymphoid cells
ILCs
intestinal inflammation
mucosal homeostasis
title T-Bet Controls Cellularity of Intestinal Group 3 Innate Lymphoid Cells
title_full T-Bet Controls Cellularity of Intestinal Group 3 Innate Lymphoid Cells
title_fullStr T-Bet Controls Cellularity of Intestinal Group 3 Innate Lymphoid Cells
title_full_unstemmed T-Bet Controls Cellularity of Intestinal Group 3 Innate Lymphoid Cells
title_short T-Bet Controls Cellularity of Intestinal Group 3 Innate Lymphoid Cells
title_sort t bet controls cellularity of intestinal group 3 innate lymphoid cells
topic T-bet
innate lymphoid cells
ILCs
intestinal inflammation
mucosal homeostasis
url https://www.frontiersin.org/articles/10.3389/fimmu.2020.623324/full
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