Atypical chemokine receptor ACKR2 controls branching morphogenesis in the developing mammary gland

Wilson, G. J. , Hewit, K. D., Pallas, K. J., Cairney, C. J., Lee, K. M., Hansell, C. A., Stein, T. and Graham, G. J. (2017) Atypical chemokine receptor ACKR2 controls branching morphogenesis in the developing mammary gland. Development, 144, pp. 74-82. (doi: 10.1242/dev.139733) (PMID:27888192) (PMCID:PMC5278629)

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Abstract

Macrophages are important regulators of branching morphogenesis during development and postnatally in the mammary gland. Regulation of macrophage dynamics during these processes can therefore have a profound impact on development. We demonstrate here that the developing mammary gland expresses high levels of inflammatory CC-chemokines, which are essential in vivo regulators of macrophage migration. We further demonstrate that the atypical chemokine receptor ACKR2, which scavenges inflammatory CC-chemokines, is differentially expressed during mammary gland development. We have previously shown that ACKR2 regulates macrophage dynamics during lymphatic vessel development. Here, we extend these observations to reveal a novel role for ACKR2 in regulating the postnatal development of the mammary gland. Specifically, we show that Ackr2−/− mice display precocious mammary gland development. This is associated with increased macrophage recruitment to the developing gland and increased density of the ductal epithelial network. These data demonstrate that ACKR2 is an important regulator of branching morphogenesis in diverse biological contexts and provide the first evidence of a role for chemokines and their receptors in postnatal development processes.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Stein, Dr Torsten and Pallas, Mr Kenny and Wilson, Dr Gillian and Lee, Miss Kit and Hansell, Dr Chris and Cairney, Dr Claire and Hewit, Dr Kay and Graham, Professor Gerard
Authors: Wilson, G. J., Hewit, K. D., Pallas, K. J., Cairney, C. J., Lee, K. M., Hansell, C. A., Stein, T., and Graham, G. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Development
Publisher:Company of Biologists
ISSN:0950-1991
ISSN (Online):1477-9129
Copyright Holders:Copyright © 2017
First Published:First published in Development 144:74-82
Publisher Policy:Reproduced under a creative commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
600961Dissecting the chemokine basis for the orchestration of the in vivo inflammatory responseGerard GrahamWellcome Trust (WELLCOME)099251/Z/12/ZIII -IMMUNOLOGY
681091The ACKR2-CCR2 axis in development and diseaseGerard GrahamMedical Research Council (MRC)MR/M019764/1III -IMMUNOLOGY