RGD Reference Report - Identification of a tissue-specific, C/EBPβ-dependent pathway of differentiation for murine peritoneal macrophages. - Rat Genome Database

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Identification of a tissue-specific, C/EBPβ-dependent pathway of differentiation for murine peritoneal macrophages.

Authors: Cain, Derek W  O'Koren, Emily G  Kan, Matthew J  Womble, Mandy  Sempowski, Gregory D  Hopper, Kristen  Gunn, Michael D  Kelsoe, Garnett 
Citation: Cain DW, etal., J Immunol. 2013 Nov 1;191(9):4665-75. doi: 10.4049/jimmunol.1300581. Epub 2013 Sep 27.
RGD ID: 40903041
Pubmed: PMID:24078688   (View Abstract at PubMed)
PMCID: PMC3808250   (View Article at PubMed Central)
DOI: DOI:10.4049/jimmunol.1300581   (Journal Full-text)

Macrophages and dendritic cells (DC) are distributed throughout the body and play important roles in pathogen detection and tissue homeostasis. In tissues, resident macrophages exhibit distinct phenotypes and activities, yet the transcriptional pathways that specify tissue-specific macrophages are largely unknown. We investigated the functions and origins of two peritoneal macrophage populations in mice: small and large peritoneal macrophages (SPM and LPM, respectively). SPM and LPM differ in their ability to phagocytose apoptotic cells, as well as in the production of cytokines in response to LPS. In steady-state conditions, SPM are sustained by circulating precursors, whereas LPM are maintained independently of hematopoiesis; however, both populations are replenished by bone marrow precursors following radiation injury. Transcription factor analysis revealed that SPM and LPM express abundant CCAAT/enhancer binding protein (C/EBP)-β. Cebpb(-/-) mice exhibit elevated numbers of SPM-like cells but lack functional LPM. Alveolar macrophages are also missing in Cebpb(-/-) mice, although macrophage populations in the spleen, kidney, skin, mesenteric lymph nodes, and liver are normal. Adoptive transfer of SPM into Cebpb(-/-) mice results in SPM differentiation into LPM, yet donor SPM do not generate LPM after transfer into C/EBPβ-sufficient mice, suggesting that endogenous LPM inhibit differentiation by SPM. We conclude that C/EBPβ plays an intrinsic, tissue-restricted role in the generation of resident macrophages.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Eosinophilia  ISOCebpb (Mus musculus)40903041; 40903041 RGD 
Eosinophilia  IMP 40903041 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cebpb  (CCAAT/enhancer binding protein beta)

Genes (Mus musculus)
Cebpb  (CCAAT/enhancer binding protein beta)

Genes (Homo sapiens)
CEBPB  (CCAAT enhancer binding protein beta)


Additional Information