T-bet controls intestinal mucosa immune responses via repression of type 2 innate lymphoid cell function

Article


Mesa, N., Schroeder, J.H., Stolarczyk, E., Gallagher, A.L., Lo, J., Bailey, C., Campbell, L., Sexl, V., MacDonald, T.T., Howard, J.K., Grencis, R.K., Powell, N. and Lord, G.M. 2018. T-bet controls intestinal mucosa immune responses via repression of type 2 innate lymphoid cell function. Mucosal Immunology. 12, pp. 51-63.
AuthorsMesa, N., Schroeder, J.H., Stolarczyk, E., Gallagher, A.L., Lo, J., Bailey, C., Campbell, L., Sexl, V., MacDonald, T.T., Howard, J.K., Grencis, R.K., Powell, N. and Lord, G.M.
Abstract

Innate lymphoid cells (ILCs) play an important role in regulating immune responses at
mucosal surfaces. The transcription factor T -bet is crucial for the function of ILC1s and
NCR+ ILC3s and constitutive deletion of T-bet prevents the development of these
subsets. Lack of T-bet in the absence of an adaptive immune system, microbiota
dependent colitis occurs due to aberrant ILC3 responses, thus T-bet expression in the
innate immune system has been considered to dampen pathogenic immune responses.
Here we show that T-bet plays an unexpected role in negatively regulating innate type 2
responses, in the context of an otherwise intact immune system. Selective loss of T -bet
in ILCs leads to the expansion and increased activity of ILC2s, which has a functionally
important impact on mucosal immunity, including enhanced protection from Trichinella
spiralis infection and inflammatory colitis. Mechanistically, we show that T-bet controls
the intestinal ILC pool through regulation of IL7 receptor signalling. These data
demonstrate that T-bet expression in ILCs acts as the key transcriptional checkpoint in regulating pathogenic versus protective mucosal immune responses, which has
significant implications for the understanding of the pathogenesis of inflammatory
bowel diseases and intestinal infections.

JournalMucosal Immunology
Journal citation12, pp. 51-63
ISSN1933-0219
Year2018
PublisherNature Publishing Group for Society of Mucosal Immunology
Publisher's version
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Digital Object Identifier (DOI)doi:10.1038/s41385-018-0092-6
Web address (URL)https://doi.org/10.1038/s41385-018-0092-6
Publication dates
Online24 Oct 2018
Publication process dates
Deposited04 Sep 2018
Accepted16 Aug 2018
Accepted16 Aug 2018
FunderWellcome Trust
Medical Research Council
National Institute for Health Research Biomedical Research Centre
Fundación Ramón Areces
British Heart Foundation
Wellcome Trust
Medical Research Council
National Institute for Health Research
Wellcome Trust
Fundación Ramón Areces
British Heart Foundation
Wellcome Trust
Copyright information© 2018 The authors.
LicenseCC BY 4.0
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