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

Tegest Aychek, Alexander Mildner, Simon Yona, Ki Wook Kim, Nardy Lampl, Shlomit Reich-Zeliger, Louis Boon, Nir Yogev, Ari Waisman, Daniel J. Cua, Steffen Jung*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


Gut homeostasis and mucosal immune defense rely on the differential contributions of dendritic cells (DC) and macrophages. Here we show that colonic CX 3 CR1 + 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.

Original languageAmerican English
Article number6525
JournalNature Communications
StatePublished - 12 Mar 2015
Externally publishedYes

Bibliographical note

Funding Information:
We would like to thank Caterina Curato and members of the Jung laboratory for help and discussion and the staff members of the Weizmann sorting facility for technical support. We thank Thomas Korn for provision of bone marrow of the IL-23 receptor-deficient mice. This work was supported by the Crohn’s and Colitis Foundation of America (CCFA), the United States—Israel Binational Science Foundation (BSF) and the Pasteur Weizmann Foundation.

Publisher Copyright:
© 2015 Macmillan Publishers Limited. All rights reserved.


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