Lee, K. M., Wilson, G. J. , Pingen, M. , Fukuoka, A. , Hansell, C. A.H., Bartolini, R., Medina-Ruiz, L. and Graham, G. J. (2019) Placental chemokine compartmentalisation: a novel mammalian molecular control mechanism. PLoS Biology, 17(5), e3000287. (doi: 10.1371/journal.pbio.3000287) (PMID:31141500) (PMCID:PMC6557524)
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Abstract
Atypical chemokine receptor 2 (ACKR2) is a chemokine-scavenging receptor. ACKR2–/–embryos display a reduction in size of a novel, to our knowledge, embryonic skin macrophage population referred to as ‘intermediate’ cells. CC chemokine receptor 2 (CCR2)–/–embryos display an identical phenotype, indicating that these cells require CCR2 to enable them to populate embryonic skin. Further analysis revealed that ACKR2–/–embryos have higher circulating concentrations of the CCR2 ligand, CC ligand 2 (CCL2); thus, ACKR2 regulates intraembryonic CCL2 levels. We show that ACKR2 is strongly expressed by trophoblasts and that it blocks movement of inflammatory chemokines, such as CCL2, from the maternal decidua into the embryonic circulation. We propose that trophoblastic ACKR2 is responsible for ensuring chemokine compartmentalisation on the maternal decidua, without which chemokines enter the embryonic circulation, disrupting gradients essential for directed intraembryonic cell migration. Overall, therefore, we describe a novel, to our knowledge, molecular mechanism whereby maternal decidual chemokines can function in a compartmentalised fashion without interfering with intraembryonic leukocyte migration. These data suggest similar functions for other atypical chemokine receptors in the placenta and indicate that defects in such receptors may have unanticipated developmental consequences.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Hansell, Dr Chris and Suzuki, Dr Ayumi and Pingen, Dr Marieke and Wilson, Dr Gillian and Medina-Ruiz, Dr Laura and Bartolini, Mr Robin and Lee, Miss Kit and Graham, Professor Gerard |
Creator Roles: | Lee, K. M.Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Writing – original draft, Writing – review and editing Wilson, G. J.Formal analysis, Investigation, Writing – original draft, Writing – review and editing Pingen, M.Conceptualization, Data curation, Formal analysis, Investigation, Writing – original draft, Writing – review and editing Hansell, C. A.H.Conceptualization, Data curation, Formal analysis, Investigation, Writing – original draft, Writing – review and editing Bartolini, R.Data curation, Formal analysis, Investigation, Writing – original draft, Writing – review and editing Medina-Ruiz, L.Data curation, Formal analysis, Investigation, Writing – original draft, Writing – review and editing Graham, G. J.Conceptualization, Data curation, Formal analysis, Funding acquisition, Methodology, Project administration, Supervision, Writing – original draft, Writing – review and editing Fukuoka, A.Formal analysis, Methodology, Writing – review and editing |
Authors: | Lee, K. M., Wilson, G. J., Pingen, M., Fukuoka, A., Hansell, C. A.H., Bartolini, R., Medina-Ruiz, L., 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: | PLoS Biology |
Publisher: | Public Library of Science |
ISSN: | 1544-9173 |
ISSN (Online): | 1545-7885 |
Published Online: | 29 May 2019 |
Copyright Holders: | Copyright © 2019 Lee et al. |
First Published: | First published in PLoS Biology 17(5): e3000287 |
Publisher Policy: | Reproduced under a Creative Commons License |
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