Sustained post-developmental T-bet expression is critical for the maintenance of type one innate lymphoid cells in vivo

Jan-Hendrik Schroeder; Luke B. Roberts; Katrin Meissl; Jon Lo; Dominika Hromadová; Kevin Hayes; Tomasz Zabinski; Emily Read; Catarina Moreira Heliodoro; Rita Antunes Dos Reis; Jane Howard; Richard Grencis; Joana F Neves; Birgit Strobl; Graham Lord

Sustained post-developmental T-bet expression is critical for the maintenance of type one innate lymphoid cells in vivo

Jan-Hendrik Schroeder, Luke B. Roberts, Katrin Meissl, Jon Lo, Dominika Hromadová, Kevin Hayes, Tomasz Zabinski, Emily Read, Catarina Moreira Heliodoro, Rita Antunes Dos Reis, Jane Howard, Richard Grencis, Joana F Neves, Birgit Strobl, Graham Lord

Research output: Contribution to journal › Article › peer-review

Abstract

Innate lymphoid cells (ILC) play a significant role in the intestinal immune response and T-bet+ CD127+ group 1 cells (ILC1) have been linked to the pathogenesis of human inflammatory bowel disease (IBD). However, the functional importance of ILC1 in the context of an intact adaptive immune response has been controversial. In this report we demonstrate that induced depletion of T-bet using a Rosa26-Cre-ERT2 model resulted in the loss of intestinal ILC1, pointing to a post-developmental requirement of T-bet expression for these cells. In contrast, neither colonic lamina propria (cLP) ILC2 nor cLP ILC3 abundance were altered upon induced deletion of T-bet. Mechanistically, we report that STAT1 or STAT4 are not required for intestinal ILC1 development and maintenance. Mice with induced deletion of T-bet and subsequent loss of ILC1 were protected from the induction of severe colitis in vivo. Hence, this study provides support for the clinical development of an IBD treatment based on ILC1 depletion via targeting T-bet or its downstream transcriptional targets.

Original language	English
Journal	Frontiers in Immunology
Publication status	Published - 29 Oct 2021

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@article{753686407d0f495ebc908e421e88db79,

title = "Sustained post-developmental T-bet expression is critical for the maintenance of type one innate lymphoid cells in vivo",

abstract = "Innate lymphoid cells (ILC) play a significant role in the intestinal immune response and T-bet+ CD127+ group 1 cells (ILC1) have been linked to the pathogenesis of human inflammatory bowel disease (IBD). However, the functional importance of ILC1 in the context of an intact adaptive immune response has been controversial. In this report we demonstrate that induced depletion of T-bet using a Rosa26-Cre-ERT2 model resulted in the loss of intestinal ILC1, pointing to a post-developmental requirement of T-bet expression for these cells. In contrast, neither colonic lamina propria (cLP) ILC2 nor cLP ILC3 abundance were altered upon induced deletion of T-bet. Mechanistically, we report that STAT1 or STAT4 are not required for intestinal ILC1 development and maintenance. Mice with induced deletion of T-bet and subsequent loss of ILC1 were protected from the induction of severe colitis in vivo. Hence, this study provides support for the clinical development of an IBD treatment based on ILC1 depletion via targeting T-bet or its downstream transcriptional targets.",

author = "Jan-Hendrik Schroeder and Roberts, {Luke B.} and Katrin Meissl and Jon Lo and Dominika Hromadov{\'a} and Kevin Hayes and Tomasz Zabinski and Emily Read and {Moreira Heliodoro}, Catarina and {Antunes Dos Reis}, Rita and Jane Howard and Richard Grencis and Neves, {Joana F} and Birgit Strobl and Graham Lord",

year = "2021",

month = oct,

day = "29",

language = "English",

journal = "Frontiers in Immunology",

issn = "1664-3224",

publisher = "Frontiers Media",

}

TY - JOUR

T1 - Sustained post-developmental T-bet expression is critical for the maintenance of type one innate lymphoid cells in vivo

AU - Schroeder, Jan-Hendrik

AU - Roberts, Luke B.

AU - Meissl, Katrin

AU - Lo, Jon

AU - Hromadová, Dominika

AU - Hayes, Kevin

AU - Zabinski, Tomasz

AU - Read, Emily

AU - Moreira Heliodoro, Catarina

AU - Antunes Dos Reis, Rita

AU - Howard, Jane

AU - Grencis, Richard

AU - Neves, Joana F

AU - Strobl, Birgit

AU - Lord, Graham

PY - 2021/10/29

Y1 - 2021/10/29

N2 - Innate lymphoid cells (ILC) play a significant role in the intestinal immune response and T-bet+ CD127+ group 1 cells (ILC1) have been linked to the pathogenesis of human inflammatory bowel disease (IBD). However, the functional importance of ILC1 in the context of an intact adaptive immune response has been controversial. In this report we demonstrate that induced depletion of T-bet using a Rosa26-Cre-ERT2 model resulted in the loss of intestinal ILC1, pointing to a post-developmental requirement of T-bet expression for these cells. In contrast, neither colonic lamina propria (cLP) ILC2 nor cLP ILC3 abundance were altered upon induced deletion of T-bet. Mechanistically, we report that STAT1 or STAT4 are not required for intestinal ILC1 development and maintenance. Mice with induced deletion of T-bet and subsequent loss of ILC1 were protected from the induction of severe colitis in vivo. Hence, this study provides support for the clinical development of an IBD treatment based on ILC1 depletion via targeting T-bet or its downstream transcriptional targets.

AB - Innate lymphoid cells (ILC) play a significant role in the intestinal immune response and T-bet+ CD127+ group 1 cells (ILC1) have been linked to the pathogenesis of human inflammatory bowel disease (IBD). However, the functional importance of ILC1 in the context of an intact adaptive immune response has been controversial. In this report we demonstrate that induced depletion of T-bet using a Rosa26-Cre-ERT2 model resulted in the loss of intestinal ILC1, pointing to a post-developmental requirement of T-bet expression for these cells. In contrast, neither colonic lamina propria (cLP) ILC2 nor cLP ILC3 abundance were altered upon induced deletion of T-bet. Mechanistically, we report that STAT1 or STAT4 are not required for intestinal ILC1 development and maintenance. Mice with induced deletion of T-bet and subsequent loss of ILC1 were protected from the induction of severe colitis in vivo. Hence, this study provides support for the clinical development of an IBD treatment based on ILC1 depletion via targeting T-bet or its downstream transcriptional targets.

M3 - Article

SN - 1664-3224

JO - Frontiers in Immunology

JF - Frontiers in Immunology

ER -

Sustained post-developmental T-bet expression is critical for the maintenance of type one innate lymphoid cells in vivo

Abstract

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