The transcription factor ZEB2 is required to maintain the tissue-specific identities of macrophages

Scott, C. L. et al. (2018) The transcription factor ZEB2 is required to maintain the tissue-specific identities of macrophages. Immunity, 49(2), 312-325.e5. (doi: 10.1016/j.immuni.2018.07.004) (PMID:30076102) (PMCID:PMC6104815)

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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.

Item Type:Articles
Additional Information:C.L.S. is supported by a Marie Curie IEF and a Sir Henry Wellcome Postdoctoral Fellowship. B.M. is supported by PHENOMIN and ERC (FP7/2007–2013 grant n° 322465), P.V. is supported by FWO, EOS (30826052 MODEL-IDI), and Methusalem (BOF16/MET_V/007), G.B. is supported by an FWO and a GOA-Ghent University grant. Y.S. is supported by the FWO and is a Marylou Ingram Scholar. M.G. is supported by an FWO, a GOA-Ghent University, and an ERC Consolidator grant.
Keywords:Clec4f-cre, Fcgr1-cre, identity, LXRα, macrophage, transcription factor, ZEB2.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Milling, Professor Simon
Authors: Scott, C. L., T'Jonck, W., Martens, L., Todorov, H., Sichien, D., Soen, B., Bonnardel, J., De Prijck, S., Vandamme, N., Cannoodt, R., Saelens, W., Vanneste, B., Toussaint, W., De Bleser, P., Takahashi, N., Vandenabeele, P., Henri, S., Pridans, C., Hume, D. A., Lambrecht, B. N., De Baetselier, P., Milling, S. W.F., Van Ginderachter, J. A., Malissen, B., Berx, G., Beschin, A., Saeys, Y., and Guilliams, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Immunity
Publisher:Elsevier
ISSN:1074-7613
ISSN (Online):1097-4180
Published Online:31 July 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Immunity 49(2):312-325.e5
Publisher Policy:Reproduced under a Creative Commons License

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