Kang, L;
Zhang, X;
Ji, L;
Kou, T;
Smith, SM;
Zhao, B;
Guo, X;
... Hu, X; + view all
(2020)
The colonic macrophage transcription factor RBP-J orchestrates intestinal immunity against bacterial pathogens.
The Journal of Experimental Medicine
, 217
(4)
, Article e20190762. 10.1084/jem.20190762.
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Abstract
Macrophages play pleiotropic roles in maintaining the balance between immune tolerance and inflammatory responses in the gut. Here, we identified transcription factor RBP-J as a crucial regulator of colonic macrophage-mediated immune responses against the enteric pathogen Citrobacter rodentium. In the immune response phase, RBP-J promoted pathogen clearance by enhancing intestinal macrophage-elicited Th17 cell immune responses, which was achieved by maintenance of C/EBPβ-dependent IL-6 production by overcoming miRNA-17∼92-mediated suppressive effects. RBP-J deficiency-associated phenotypes could be genetically corrected by further deleting miRNA-17∼92 in macrophages. In the late phase, noneradicated pathogens in RBP-J KO mice recruited abundant IL-1β-expressing CD64+Ly6C+ colonic macrophages and thereby promoted persistence of ILC3-derived IL-22 to compensate for the impaired innate and adaptive immune responses, leading to ultimate clearance of pathogens. These results demonstrated that colonic macrophage-intrinsic RBP-J dynamically orchestrates intestinal immunity against pathogen infections by interfacing with key immune cells of T and innate lymphoid cell lineages.
| Type: | Article |
|---|---|
| Title: | The colonic macrophage transcription factor RBP-J orchestrates intestinal immunity against bacterial pathogens |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1084/jem.20190762 |
| Publisher version: | https://doi.org/10.1084/jem.20190762 |
| Language: | English |
| Additional information: | This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/) |
| 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/10097847 |
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