TY  - JOUR
N1  - 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/)
UR  - https://doi.org/10.1084/jem.20190762
A1  - Kang, L
A1  - Zhang, X
A1  - Ji, L
A1  - Kou, T
A1  - Smith, SM
A1  - Zhao, B
A1  - Guo, X
A1  - Pineda-Torra, I
A1  - Wu, L
A1  - Hu, X
Y1  - 2020/01/16/
AV  - public
N2  - 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/EBP?-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-1?-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.
ID  - discovery10097847
VL  - 217
IS  - 4
JF  - The Journal of Experimental Medicine
TI  - The colonic macrophage transcription factor RBP-J orchestrates intestinal immunity against bacterial pathogens
ER  -