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Bhlhe40 and Bhlhe41 transcription factors regulate alveolar macrophage self-renewal and identity

Item Type:Article
Title:Bhlhe40 and Bhlhe41 transcription factors regulate alveolar macrophage self-renewal and identity
Creators Name:Rauschmeier, R. and Gustafsson, C. and Reinhardt, A. and A-Gonzalez, N. and Tortola, L. and Cansever, D. and Subramanian, S. and Taneja, R. and Rossner, M.J. and Sieweke, M.H. and Greter, M. and Månsson, R. and Busslinger, M. and Kreslavsky, T.
Abstract:Tissues in multicellular organisms are populated by resident macrophages, which perform both generic and tissue-specific functions. The latter are induced by signals from the microenvironment and rely on unique tissue-specific molecular programs requiring the combinatorial action of tissue-specific and broadly expressed transcriptional regulators. Here, we identify the transcription factors Bhlhe40 and Bhlhe41 as novel regulators of alveolar macrophages (AMs)-a population that provides the first line of immune defense and executes homeostatic functions in lung alveoli. In the absence of these factors, AMs exhibited decreased proliferation that resulted in a severe disadvantage of knockout AMs in a competitive setting. Gene expression analyses revealed a broad cell-intrinsic footprint of Bhlhe40/Bhlhe41 deficiency manifested by a downregulation of AM signature genes and induction of signature genes of other macrophage lineages. Genome-wide characterization of Bhlhe40 DNA binding suggested that these transcription factors directly repress the expression of lineage-inappropriate genes in AMs. Taken together, these results identify Bhlhe40 and Bhlhe41 as key regulators of AM self-renewal and guardians of their identity.
Keywords:Alveolar Macrophages, Bhlhe40, Bhlhe41, Self-Renewal, Tissue-Resident Macrophages, Animals, Mice
Source:EMBO Journal
Publisher:EMBO Press
Page Range:e101233
Date:1 October 2019
Official Publication:https://doi.org/10.15252/embj.2018101233
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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