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.
The colonic macrophage transcription factor RBP-J orchestrates intestinal immunity against bacterial pathogens
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Lan Kang, Xiang Zhang, Liangliang Ji, Tiantian Kou, Sinead M. Smith, Baohong Zhao, Xiaohuan Guo, Inés Pineda-Torra, Li Wu, Xiaoyu Hu; The colonic macrophage transcription factor RBP-J orchestrates intestinal immunity against bacterial pathogens. J Exp Med 6 April 2020; 217 (4): e20190762. doi: https://doi.org/10.1084/jem.20190762
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