Interferon Regulatory Factor 1 (IRF-1) Promotes Intestinal Group 3 Innate Lymphoid Responses During Citrobacter Rodentium Infection

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Sep 29

PMID 36175404

Authors

Angelika Schmalzl

Tamara Leupold

Lucas Kreiss

Maximilian Waldner

Sebastian Schurmann

Markus F Neurath

Christoph Becker

Stefan Wirtz

Affiliations

Soon will be listed here.

Abstract

Group 3 innate lymphoid cells (ILC3s) are crucial mediators of immunity and epithelial barrier function during immune responses against extracellular bacteria. Here, we identify Interferon regulatory factor 1 (IRF-1), a transcription factor previously associated with type 1 immunity, as an essential regulator of intestinal ILC3 accumulation and effector cytokine production. We demonstrate that IRF-1 is upregulated in the context of infection with the enteropathogen Citrobacter rodentium and that its presence is central for anatomical containment and prevention of pathogen dissemination. We furthermore show that IRF-1 is required in order for intestinal ILC3s to produce large amounts of the protective effector cytokine IL-22 early in the course of infection. On a molecular level, our data indicate that IRF-1 controls ILC3 numbers and their activation by direct transcriptional regulation of the IL-12Rβ1 chain, thereby allowing ILCs to physiologically respond to IL-23 stimulation.

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