| First Author | Kang L | Year | 2020 |
| Journal | J Exp Med | Volume | 217 |
| Issue | 4 | PubMed ID | 31944217 |
| Mgi Jnum | J:289661 | Mgi Id | MGI:6432465 |
| Doi | 10.1084/jem.20190762 | Citation | Kang L, et al. (2020) The colonic macrophage transcription factor RBP-J orchestrates intestinal immunity against bacterial pathogens. J Exp Med 217(4) |
| abstractText | 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/EBPbeta-dependent IL-6 production by overcoming miRNA-17 approximately 92-mediated suppressive effects. RBP-J deficiency-associated phenotypes could be genetically corrected by further deleting miRNA-17 approximately 92 in macrophages. In the late phase, noneradicated pathogens in RBP-J KO mice recruited abundant IL-1beta-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. |
