Chemokine receptors coordinately regulate macrophage dynamics and mammary gland development

Wilson, G. J. , Fukuoka, A. , Love, S. R., Kim, J., Pingen, M., Hayes, A. J. and Graham, G. J. (2020) Chemokine receptors coordinately regulate macrophage dynamics and mammary gland development. Development, (doi: 10.1242/dev.187815) (PMID:32467242) (Early Online Publication)

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Abstract

Macrophages are key regulators of developmental processes, including those involved in mammary gland development. We previously demonstrated that the atypical chemokine receptor, ACKR2, contributes to control of ductal epithelial branching in the developing mammary gland by regulating macrophage dynamics. ACKR2 is a chemokine-scavenging receptor, which mediates its effects through collaboration with inflammatory chemokine receptors (iCCRs). Here we reveal reciprocal regulation of branching morphogenesis in the mammary gland, whereby stromal ACKR2 modulates levels of the shared ligand CCL7 to control the movement of a key population of CCR1-expressing macrophages to the ductal epithelium. In addition, estrogen, which is essential for ductal elongation during puberty, upregulates CCR1 expression on macrophages. The age at which girls develop breasts is decreasing, which raises the risk of diseases including breast cancer. This study presents a previously unknown mechanism controlling the rate of mammary gland development during puberty and highlights potential therapeutic targets.

Item Type:Articles
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:Love, Samantha and Hayes, Mr Alan and Pingen, Dr Marieke and Suzuki, Dr Ayumi and Wilson, Dr Gillian and Graham, Professor Gerard
Authors: Wilson, G. J., Fukuoka, A., Love, S. R., Kim, J., Pingen, M., Hayes, A. J., and Graham, G. J.
College/School: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
Published Online:28 May 2020
Copyright Holders:Copyright © 2020 The Company of Biologists Ltd
First Published:First published in Development 2020
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
171627The ACKR2-CCR2 axis in development and diseaseGerard GrahamMedical Research Council (MRC)MR/M019764/1III - Immunology
167227Dissecting the chemokine basis for the orchestration of the in vivo inflammatory responseGerard GrahamWellcome Trust (WELLCOTR)099251/Z/12/ZIII - Immunology