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Macrophages inhibit and enhance endometriosis depending on their origin
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Hogg, Chloe, Panir, Kavita, Dhami, Priya, Rosser, Matthew, Mack, Matthias, Soong, Daniel, Pollard, Jeffrey W., Jenkins, Stephen J., Horne, Andrew W. and Greaves, Erin (2021) Macrophages inhibit and enhance endometriosis depending on their origin. Proceedings of the National Academy of Sciences of the United States of America, 118 (6). e2013776118. doi:10.1073/pnas.2013776118 ISSN 0027-8424.
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Official URL: https://doi.org/10.1073/pnas.2013776118
Abstract
Macrophages are intimately involved in the pathophysiology of endometriosis, a chronic inflammatory disorder characterized by the growth of endometrial-like tissue (lesions) outside the uterus. By combining genetic and pharmacological monocyte and macrophage depletion strategies we determined the ontogeny and function of macrophages in a mouse model of induced endometriosis. We demonstrate that lesion-resident macrophages are derived from eutopic endometrial tissue, infiltrating large peritoneal macrophages (LpM) and monocytes. Furthermore, we found endometriosis to trigger continuous recruitment of monocytes and expansion of CCR2+ LpM. Depletion of eutopic endometrial macrophages results in smaller endometriosis lesions, whereas constitutive inhibition of monocyte recruitment significantly reduces peritoneal macrophage populations and increases the number of lesions. Reprogramming the ontogeny of peritoneal macrophages such that embryo-derived LpM are replaced by monocyte-derived LpM decreases the number of lesions that develop. We propose a putative model whereby endometrial macrophages are “proendometriosis” while newly recruited monocyte-derived macrophages, possibly in LpM form, are “antiendometriosis.” These observations highlight the importance of monocyte-derived macrophages in limiting disease progression.
Item Type: | Journal Article | ||||||||||||||||||
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Subjects: | Q Science > QR Microbiology R Medicine > RG Gynecology and obstetrics |
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Macrophages, Macrophages -- Activation, Endometriosis, Endometrium -- Diseases -- Diagnosis | ||||||||||||||||||
Journal or Publication Title: | Proceedings of the National Academy of Sciences of the United States of America | ||||||||||||||||||
Publisher: | National Academy of Sciences | ||||||||||||||||||
ISSN: | 0027-8424 | ||||||||||||||||||
Official Date: | 9 February 2021 | ||||||||||||||||||
Dates: |
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Volume: | 118 | ||||||||||||||||||
Number: | 6 | ||||||||||||||||||
Article Number: | e2013776118 | ||||||||||||||||||
DOI: | 10.1073/pnas.2013776118 | ||||||||||||||||||
Status: | Peer Reviewed | ||||||||||||||||||
Publication Status: | Published | ||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||
Date of first compliant deposit: | 18 January 2021 | ||||||||||||||||||
Date of first compliant Open Access: | 24 February 2021 | ||||||||||||||||||
RIOXX Funder/Project Grant: |
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