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Title: Bhlhe40 mediates tissue-specific control of macrophage proliferation in homeostasis and type 2 immunity
Authors: Jarjour, NN
Schwarzkopf, EA
Bradstreet, TR
Shchukina, I
Lin, CC
Huang, SCC
Lai, CW
Cook, ME
Taneja, R 
Stappenbeck, TS
Randolph, GJ
Artyomov, MN
Urban, JF
Edelson, BT
Issue Date: 1-Jan-2019
Publisher: Springer Science and Business Media LLC
Citation: Jarjour, NN, Schwarzkopf, EA, Bradstreet, TR, Shchukina, I, Lin, CC, Huang, SCC, Lai, CW, Cook, ME, Taneja, R, Stappenbeck, TS, Randolph, GJ, Artyomov, MN, Urban, JF, Edelson, BT (2019-01-01). Bhlhe40 mediates tissue-specific control of macrophage proliferation in homeostasis and type 2 immunity. Nature Immunology. ScholarBank@NUS Repository.
Abstract: © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc. 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.
Source Title: Nature Immunology
ISSN: 15292908
DOI: 10.1038/s41590-019-0382-5
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