{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Jarjour NN"],"funding":["NCATS NIH HHS","NIAID NIH HHS"],"pagination":["687-700"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6531324"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["20(6)"],"pubmed_abstract":["Most tissue-resident macrophage populations develop during embryogenesis, self-renew in the steady state and expand during type 2 immunity. Whether shared mechanisms regulate the proliferation of macrophages in homeostasis and disease is unclear. Here we found that the transcription factor Bhlhe40 was required in a cell-intrinsic manner for the self-renewal and maintenance of large peritoneal macrophages (LPMs), but not that of other tissue-resident macrophages. Bhlhe40 was necessary for the proliferation, but not the polarization, of LPMs in response to the cytokine IL-4. During infection with the helminth Heligmosomoides polygyrus bakeri, Bhlhe40 was required for cell cycling of LPMs. Bhlhe40 repressed the expression of genes encoding the transcription factors c-Maf and Mafb and directly promoted expression of transcripts encoding cell cycle-related proteins to enable the proliferation of LPMs. In LPMs, Bhlhe40 bound to genomic sites co-bound by the macrophage lineage-determining factor PU.1 and to unique sites, including Maf and loci encoding cell-cycle-related proteins. Our findings demonstrate a tissue-specific control mechanism that regulates the proliferation of resident macrophages in homeostasis and type 2 immunity."],"journal":["Nature immunology"],"pubmed_title":["Bhlhe40 mediates tissue-specific control of macrophage proliferation in homeostasis and type 2 immunity."],"pmcid":["PMC6531324"],"funding_grant_id":["R01 AI132653","UL1 TR002345","T32 AI007163","R01 AI113118"],"pubmed_authors":["Shchukina I","Randolph GJ","Stappenbeck TS","Urban JF","Lin CC","Cook ME","Edelson BT","Bradstreet TR","Schwarzkopf EA","Jarjour NN","Huang SC","Lai CW","Taneja R","Artyomov MN"],"additional_accession":[]},"is_claimable":false,"name":"Bhlhe40 mediates tissue-specific control of macrophage proliferation in homeostasis and type 2 immunity.","description":"Most tissue-resident macrophage populations develop during embryogenesis, self-renew in the steady state and expand during type 2 immunity. Whether shared mechanisms regulate the proliferation of macrophages in homeostasis and disease is unclear. Here we found that the transcription factor Bhlhe40 was required in a cell-intrinsic manner for the self-renewal and maintenance of large peritoneal macrophages (LPMs), but not that of other tissue-resident macrophages. Bhlhe40 was necessary for the proliferation, but not the polarization, of LPMs in response to the cytokine IL-4. During infection with the helminth Heligmosomoides polygyrus bakeri, Bhlhe40 was required for cell cycling of LPMs. Bhlhe40 repressed the expression of genes encoding the transcription factors c-Maf and Mafb and directly promoted expression of transcripts encoding cell cycle-related proteins to enable the proliferation of LPMs. In LPMs, Bhlhe40 bound to genomic sites co-bound by the macrophage lineage-determining factor PU.1 and to unique sites, including Maf and loci encoding cell-cycle-related proteins. Our findings demonstrate a tissue-specific control mechanism that regulates the proliferation of resident macrophages in homeostasis and type 2 immunity.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Jun","modification":"2024-02-15T02:07:14.64Z","creation":"2019-11-12T08:04:31Z"},"accession":"S-EPMC6531324","cross_references":{"pubmed":["31061528"],"doi":["10.1038/s41590-019-0382-5"]}}