The Transcription Factor T-bet Regulates Intestinal Inflammation Mediated by Interleukin-7 Receptor+ Innate Lymphoid Cells

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2012 Oct 16

PMID 23063332

Citations 191

Authors

Nick Powell

Alan W Walker

Emilie Stolarczyk

James B Canavan

M Refik Gokmen

Ellen Marks

Ian Jackson

Ahmed Hashim

Michael A Curtis

Richard G Jenner

Jane K Howard

Julian Parkhill

Thomas T Macdonald

Graham M Lord

Affiliations

Soon will be listed here.

Abstract

Mice lacking the transcription factor T-bet in the innate immune system develop microbiota-dependent colitis. Here, we show that interleukin-17A (IL-17A)-producing IL-7Rα(+) innate lymphoid cells (ILCs) were potent promoters of disease in Tbx21(-/-)Rag2(-/-) ulcerative colitis (TRUC) mice. TNF-α produced by CD103(-)CD11b(+) dendritic cells synergized with IL-23 to drive IL-17A production by ILCs, demonstrating a previously unrecognized layer of cellular crosstalk between dendritic cells and ILCs. We have identified Helicobacter typhlonius as a key disease trigger driving excess TNF-α production and promoting colitis in TRUC mice. Crucially, T-bet also suppressed the expression of IL-7R, a key molecule involved in controlling intestinal ILC homeostasis. The importance of IL-7R signaling in TRUC disease was highlighted by the dramatic reduction in intestinal ILCs and attenuated colitis following IL-7R blockade. Taken together, these data demonstrate the mechanism by which T-bet regulates the complex interplay between mucosal dendritic cells, ILCs, and the intestinal microbiota.

Citing Articles

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