New understanding of mammary gland development
Published: 17 July 2020
Scientists from the Institute's Chemokine Research Group have shown that chemokine receptors coordinate macrophage movement to control the development of the mammary gland during puberty.
Scientists from the Institute's Chemokine Research Group (CRG) have shown that chemokine receptors coordinate macrophage movement to control the development of the mammary gland during puberty.
Back in 2017, the group found that mice without the atypical chemokine receptor ACKR2, which scavenges inflammatory chemokines, underwent early mammary gland development.
This was the first time that a chemokine receptor was shown to control postnatal development.
They showed that ACKR2 was expressed by fibroblasts and controlled macrophages and branching in the mammary gland.
However, this raised further questions as ACKR2 itself is non-signalling but shares chemokine ligands with inflammatory receptors.
In the current study, published in Development, individual and compound receptor deficient mice developed by the CRG previously were used to find out which receptor works with ACKR2.
The reciprocal receptor was identified as CCR1, as deficient mice had delayed mammary gland development.
Their research also showed that the macrophage regulated by ACKR2 and CCR1 in the mammary gland is a small but important population which expresses CD206 (Mannose receptor).
They found the key chemokine responsible for recruiting these macrophages and driving branching was CCL7, and also showed that CCR1 expression on macrophages can be increased by exposure to estrogen and endocrine disrupters such as BPA.
Dr Gill Wilson explained: "Throughout the world the age at which puberty begins continues to fall. This has important health implications as girls who develop before the age of 11 are 20 per cent more likely to develop breast cancer in later life.
"In our study we provide an immunological mechanism that helps us understand the how the timing of development is regulated during puberty and may allow therapeutic intervention."
Chemokine receptors coordinately regulate macrophage dynamics and mammary gland development
- Gillian J. Wilson, Ayumi Fukuoka, Samantha R. Love, Jiwon Kim, Marieke Pingen, Alan J. Hayes, Gerard J. Graham.
- Development 2020 147 dev187815 doi: 10.1242/dev.187815, Published 17 June 2020
First published: 17 July 2020