The colonic macrophage transcription factor RBP-J orchestrates intestinal immunity against bacterial pathogens. Academic Article uri icon

Overview

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.

publication date

  • April 6, 2020

Research

keywords

  • Citrobacter rodentium
  • Colon
  • Enterobacteriaceae Infections
  • Host-Pathogen Interactions
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein
  • Macrophages

Identity

PubMed Central ID

  • PMC7144519

Scopus Document Identifier

  • 85077941314

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2012.08.026

PubMed ID

  • 31944217

Additional Document Info

volume

  • 217

issue

  • 4