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

TY - JOUR

T1 - T-Bet Controls Cellularity of Intestinal Group 3 Innate Lymphoid Cells

AU - Schroeder, Jan Hendrik

AU - Meissl, Katrin

AU - Hromadová, Dominika

AU - Lo, Jonathan W.

AU - Neves, Joana F.

AU - Howard, Jane K.

AU - Helmby, Helena

AU - Powell, Nick

AU - Strobl, Birgit

AU - Lord, Graham M.

N1 - Funding Information: This study was supported by grants awarded by the Wellcome Trust (GL, 091009) and the Medical Research Council (GL, MR/ M003493/1; GL, MR/K002996/1; JH, MR/K002996/1). Research was also supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy’s and St Thomas and King’s College London (GL), the Austrian Science Fund (BS, FWF, SFB-F6101), the Welcome Trust (NP, JL, WT101159) and the NIHR Imperial Biomedical Research Center (NP, JL, BRC). JN acknowledges a RCUK/UKRI Rutherford Fund fellowship (MR/R024812/1). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. Publisher Copyright: © Copyright © 2021 Schroeder, Meissl, Hromadová, Lo, Neves, Howard, Helmby, Powell, Strobl and Lord. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/2/2

Y1 - 2021/2/2

N2 - 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.

AB - 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.

KW - ILCs

KW - innate lymphoid cells

KW - intestinal inflammation

KW - mucosal homeostasis

KW - T-bet

UR - http://www.scopus.com/inward/record.url?scp=85100912108&partnerID=8YFLogxK

U2 - 10.3389/fimmu.2020.623324

DO - 10.3389/fimmu.2020.623324

M3 - Article

AN - SCOPUS:85100912108

SN - 1664-3224

VL - 11

JO - Frontiers in Immunology

JF - Frontiers in Immunology

M1 - 623324

ER -