Macrophages inhibit and enhance endometriosis depending on their origin.
lesion
ontogeny
phenotype
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
09 02 2021
09 02 2021
Historique:
entrez:
4
2
2021
pubmed:
5
2
2021
medline:
24
6
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33536334
pii: 2013776118
doi: 10.1073/pnas.2013776118
pmc: PMC8017702
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
Chemokine CCL2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Medical Research Council
ID : MR/N022556/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S002456/2
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 101067/Z/12/Z
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M009238/1
Pays : United Kingdom
Informations de copyright
Copyright © 2021 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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