The Transcription Factor ZEB2 Is Required to Maintain the Tissue-Specific Identities of Macrophages
Charlotte L. Scott
(1, 2, 3)
,
Wouter t'Jonck
(1, 2)
,
Liesbet Martens
(2)
,
Helena Todorov
(4, 2)
,
Dorine Sichien
(5, 2, 1)
,
Bieke Soen
(6, 7, 2)
,
Johnny Bonnardel
(1, 2)
,
Sofie de Prijck
(1, 2)
,
Niels Vandamme
(6, 7, 2)
,
Robrecht Cannoodt
(8, 2)
,
Wouter Saelens
(2)
,
Bavo Vanneste
(1, 2)
,
Wendy Toussaint
(9)
,
Pieter de Bleser
(2)
,
Nozomi Takahashi
(2)
,
Peter Vandenabeele
(2)
,
Sandrine Henri
(10)
,
Clare Pridans
,
David A. Hume
(11)
,
Bart N. Lambrecht
(1, 12)
,
Patrick de Baetselier
(13, 14)
,
Simon W. F. Milling
(3)
,
Jo A. van Ginderachter
,
Bernard Malissen
(10)
,
Geert Berx
(6, 7)
,
Alain Beschin
,
Yvan Saeys
(4, 15)
,
Martin Guilliams
(1)
1
IRC -
VIB-UGent Center for Inflammation Research [Gand, Belgique]
2 Department of Biomedical Molecular Biology [Ghent]
3 College of Medical, Veterinary and Life Sciences [Glasgow]
4 Data Mining and Modelling for Biomedicine [Ghent, Belgium]
5 Unit of Immunoregulation and Mucosal Immunology [Ghent, Belgium]
6 Molecular and Cellular Oncology Lab, Inflammation Research Center, VIB
7 Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG)
8 Ghent University Hospital
9 Department of Cell Biology and Genetics
10 CIML - Centre d'Immunologie de Marseille - Luminy
11 The Roslin Institute and Royal (Dick) School of Veterinary Studies
12 Department of Respiratory Medicine
13 Vrije Universiteit Brussel - Myeloid Cell immunology Laboratory
14 Laboratory of cellular & Molecular Immunology [Vrije Universiteit Brussel]
15 Department of Applied Mathematics, Computer Science and Statistics [Ghent, Belgium]
2 Department of Biomedical Molecular Biology [Ghent]
3 College of Medical, Veterinary and Life Sciences [Glasgow]
4 Data Mining and Modelling for Biomedicine [Ghent, Belgium]
5 Unit of Immunoregulation and Mucosal Immunology [Ghent, Belgium]
6 Molecular and Cellular Oncology Lab, Inflammation Research Center, VIB
7 Department of Biomedical Molecular Biology, Cancer Research Institute Ghent (CRIG)
8 Ghent University Hospital
9 Department of Cell Biology and Genetics
10 CIML - Centre d'Immunologie de Marseille - Luminy
11 The Roslin Institute and Royal (Dick) School of Veterinary Studies
12 Department of Respiratory Medicine
13 Vrije Universiteit Brussel - Myeloid Cell immunology Laboratory
14 Laboratory of cellular & Molecular Immunology [Vrije Universiteit Brussel]
15 Department of Applied Mathematics, Computer Science and Statistics [Ghent, Belgium]
Peter Vandenabeele
- Fonction : Auteur
- PersonId : 761774
- ORCID : 0000-0002-6669-8822
Sandrine Henri
- Fonction : Auteur
- PersonId : 758398
- ORCID : 0000-0002-8980-9193
- IdRef : 143029851
Clare Pridans
- Fonction : Auteur
Jo A. van Ginderachter
- Fonction : Auteur
Bernard Malissen
- Fonction : Auteur
- PersonId : 739259
- IdHAL : bernard-malissen
- IdRef : 03049690X
Alain Beschin
- Fonction : Auteur
Résumé
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 LXR alpha, 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.