The Transcription Factor ZEB2 Is Required to Maintain the Tissue-Specific Identities of Macrophages

Charlotte L Scott, Wouter T'Jonck, Liesbet Martens, Helena Todorov, Dorine Sichien, Bieke Soen, Johnny Bonnardel, Sofie De Prijck, Niels Vandamme, Robrecht Cannoodt, Wouter Saelens, Bavo Vanneste, Wendy Toussaint, Pieter De Bleser, Nozomi Takahashi, Peter Vandenabeele, Sandrine Henri, Clare Pridans, David A Hume, Bart N LambrechtPatrick De Baetselier, Simon W F Milling, Jo A Van Ginderachter, Bernard Malissen, Geert Berx, Alain Beschin, Yvan Saeys, Martin Guilliams

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Heterogeneity between different macrophage populations has become a defining feature of this lineage. However, the conserved factors defining macrophages remain largely unknown. The transcription factor ZEB2 is best described for its role in epithelial to mesenchymal transition; however, its role within the immune system is only now being elucidated. We show here that Zeb2 expression is a conserved feature of macrophages. Using Clec4f-cre, Itgax-cre, and Fcgr1-cre mice to target five different macrophage populations, we found that loss of ZEB2 resulted in macrophage disappearance from the tissues, coupled with their subsequent replenishment from bone-marrow precursors in open niches. Mechanistically, we found that ZEB2 functioned to maintain the tissue-specific identities of macrophages. In Kupffer cells, ZEB2 achieved this by regulating expression of the transcription factor LXRα removal of which recapitulated the loss of Kupffer cell identity and disappearance. Thus, ZEB2 expression is required in macrophages to preserve their tissue-specific identities. Scott et al. demonstrate that ZEB2 is critical for maintaining the tissue identities of macrophages. Loss of ZEB2 results in tissue-specific changes in different macrophage populations and their subsequent disappearance. In Kupffer cells, ZEB2 maintains LXRα expression, loss of which reproduces the change in Kupffer cell identity and their disappearance.

Original languageEnglish
Pages (from-to)312-325.e5
JournalIMMUNITY
Volume49
Issue number2
DOIs
Publication statusPublished - 21 Aug 2018

Bibliographical note

Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Keywords

  • Clec4f-cre
  • Fcgr1-cre
  • Identity
  • LXRα
  • Macrophage
  • Transcription Factor
  • ZEB2

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