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, 147(12), dev187815. (doi: 10.1242/dev.187815) (PMID:32467242) (PMCID:PMC7328164)
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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: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Love, Samantha and Suzuki, Dr Ayumi and Hayes, Mr Alan and Pingen, Dr Marieke 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 > School of Infection & Immunity |
| Research Centre: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology |
| 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 147(12): dev187815 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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