Fukuoka, A., Wilson, G. J., Pitmon, E., Koumbas Foley, L., Johnsson, H., Pingen, M. and Graham, G. J. (2024) Disruption of placental ACKR3 effects embryo, and offspring, growth and hematopoietic development. Development, 151(4), dev202333. (doi: 10.1242/dev.202333) (PMID:38300826)
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Abstract
ACKR3 scavenges and degrades the stem cell recruiting chemokine CXCL12 which is essential for proper embryonic, and in particular hematopoietic development. Here we demonstrate strong expression of ACKR3 on trophoblasts. Using a maternally-administered pharmacological blocker, and Cre-mediated genetic approaches, we demonstrate that trophoblast ACKR3 is essential for preventing movement of CXCL12 from the mother to the embryo with elevated plasma CXCL12 levels being detected in embryos from ACKR3-blocker treated mothers. Mice born to mothers treated with the blocker are lighter and shorter than those born to vehicle-treated mothers and, in addition, display profound anaemia associated with a markedly reduced bone marrow hematopoietic stem cell population. Importantly, whilst the hematopoietic abnormalities are corrected as mice age, our studies reveal a postnatal window during which offspring of ACKR3 blocker treated mice are unable to mount effective inflammatory responses to inflammatory/infectious stimuli. Overall, these data demonstrate that ACKR3 is essential for preventing CXCL12 transfer from mother to embryo and for ensuring properly regulated CXCL12 control over the development of the hematopoietic system.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was supported by grants to GJG from the Wellcome Trust (217093/Z/19/Z) and the MRC (MR/V010972/1). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Koumbas Foley, Lily and Pingen, Dr Marieke and Johnsson, Dr Hanna and Graham, Professor Gerard and Pitmon, Miss Elise |
| Authors: | Fukuoka, A., Wilson, G. J., Pitmon, E., Koumbas Foley, L., Johnsson, H., Pingen, M., and Graham, G. J. |
| College/School: | College of Medical Veterinary and Life Sciences College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Development |
| Publisher: | Company of Biologists |
| ISSN: | 0950-1991 |
| ISSN (Online): | 1477-9129 |
| Published Online: | 01 February 2024 |
| Copyright Holders: | Copyright © 2024. Published by The Company of Biologists Ltd |
| First Published: | First published in Development 151(4):dev202333 |
| Publisher Policy: | Reproduced under a Creative Commons license |
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