The transcription factor EGR2 is indispensable for tissue-specific imprinting of alveolar macrophages in health and tissue repair

McCowan, J. et al. (2021) The transcription factor EGR2 is indispensable for tissue-specific imprinting of alveolar macrophages in health and tissue repair. Science Immunology, 6(65), eabj2132. (doi: 10.1126/sciimmunol.abj2132) (PMID:34797692) (PMCID:PMC7612216)

Abstract

Alveolar macrophages are important for maintaining lung homeostasis and protecting the lungs against injury and respiratory pathogens, tissue-specific functions that are acquired in response to local environmental signals. McCowan et al. identify expression of the transcription factor EGR2 as a specific feature of both mouse and human alveolar macrophages, which is required for acquisition of the core alveolar macrophage phenotypic identity. In mice, deletion of EGR2 in myeloid cells impaired effective clearance of bacteria from the respiratory tract and tissue repair after sterile injury that required monocyte-dependent alveolar macrophage repopulation. EGR2 expression was induced by the cytokines TGF-β and GM-CSF in a PPAR-γ–dependent manner, highlighting a role for EGR2 downstream of other key signals that together coordinate the alveolar macrophage functional program.

• Item Type: Articles
• Additional Information: This research was funded by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society [Grant number 206234/Z/17/Z to C.C.B]. CGH is supported by a University of Edinburgh Chancellor’s Fellowship and CGH and RC are supported by Worldwide Cancer Research. The Lyz2Cre.Egr2fl/fl line was originally generated with funding from the Medical Research Council UK (MR/L008076/1 to S.J.J). GRJ is funded by a Wellcome Trust Clinical Career Development Fellowship (220725/Z/20/Z). SRW is funded by a Wellcome Trust Senior Clinical Fellowship (209220). PTKS received funding from the MRC (MR/N024524/1). FF and LMC are funded by Cancer Research UK core funding (A23983 & A31287), and Breast Cancer Now (2019DecPR1424). This research was funded in whole or in part by The Wellcome Trust [Grant number 206234/Z/17/Z], a cOAlition S organization.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Carlin, Dr Leo
• Authors: McCowan, J., Fercoq, F., Kirkwood, P. M., T’Jonck, W., Hegarty, L. M., Mawer, C. M., Cunningham, R., Mirchandani, A. S., Hoy, A., Humphries, D. C., Jones, G.-R., Hansen, C. G., Hirani, N., Jenkins, S. J., Henri, S., Malissen, B., Walmsley, S. R., Dockrell, D. H., Saunders, P. T. K., Carlin, L. M., and Bain, C. C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Science Immunology
• Publisher: American Association for the Advancement of Science (AAAS)
• ISSN: 2470-9468
• ISSN (Online): 2470-9468
• Published Online: 19 November 2021
• Copyright Holders: Copyright © 2021 American Association for the Advancement of Science
• First Published: First published in Science Immunology 6(65):eabj2132
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher