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IL-23-mediated mononuclear phagocyte crosstalk protects mice from Citrobacter rodentium-induced colon immunopathology.

Aychek, T; Mildner, A; Yona, S; Kim, K-W; Lampl, N; Reich-Zeliger, S; Boon, L; ... Jung, S; + view all (2015) IL-23-mediated mononuclear phagocyte crosstalk protects mice from Citrobacter rodentium-induced colon immunopathology. Nature Communications , 6 , Article 6525. 10.1038/ncomms7525. Green open access

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Abstract

Gut homeostasis and mucosal immune defense rely on the differential contributions of dendritic cells (DC) and macrophages. Here we show that colonic CX3CR1(+) mononuclear phagocytes are critical inducers of the innate response to Citrobacter rodentium infection. Specifically, the absence of IL-23 expression in macrophages or CD11b(+) DC results in the impairment of IL-22 production and in acute lethality. Highlighting immunopathology as a death cause, infected animals are rescued by the neutralization of IL-12 or IFNγ. Moreover, mice are also protected when the CD103(+) CD11b(-) DC compartment is rendered deficient for IL-12 production. We show that IL-12 production by colonic CD103(+) CD11b(-) DC is repressed by IL-23. Collectively, in addition to its role in inducing IL-22 production, macrophage-derived or CD103(-) CD11b(+) DC-derived IL-23 is required to negatively control the otherwise deleterious production of IL-12 by CD103(+) CD11b(-) DC. Impairment of this critical mononuclear phagocyte crosstalk results in the generation of IFNγ-producing former TH17 cells and fatal immunopathology.

Type: Article
Title: IL-23-mediated mononuclear phagocyte crosstalk protects mice from Citrobacter rodentium-induced colon immunopathology.
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/ncomms7525
Publisher version: http://dx.doi.org/ 10.1038/ncomms7525
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the & Copyright © 2015 Macmillan Publishers Limited. All rights reserved.credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Animals, Antigens, CD, Antigens, CD11b, Citrobacter rodentium, Colon, Dendritic Cells, Enterobacteriaceae Infections, Gene Expression Regulation, Homeostasis, Immunity, Innate, Immunity, Mucosal, Integrin alpha Chains, Interferon-gamma, Interleukin-12, Interleukin-23, Interleukins, Intestinal Mucosa, Macrophages, Mice, Mice, Transgenic, Monocytes, Receptors, Chemokine, Signal Transduction, Survival Analysis, Th17 Cells
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1464093
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