The dual roles of uterine monocytes in regulation of tissue homeostasis throughout reproductive cycles in health and disease
Abstract
Inflammation occurs during the recurring cycles of tissue degradation, repair and remodeling in the uterus, but the mechanisms by which the immune system contributes to uterine tissue integrity are unclear. We reveal that uterine monocytes have dual roles in both tissue remodeling and inflammation, depending on the reproductive cycle stage. Circulating inflammatory monocytes infiltrated the uterus before their differentiation into proinflammatory or pro-repair macrophages, depending on interferon-γ and transforming growth factor-β, respectively. Human monocyte numbers peaked before the window of implantation, when an inflammatory environment is required for embryo implantation. Uterine monocytes exhibited cytotoxic properties, regulating epithelial cell apoptosis. Bioinformatic analyses of receptor–ligand interactions indicated that monocytes dominated interactions between myeloid cells and fibroblasts. These pathways were disrupted in uterine fibrosis, marked by excess inflammatory monocytes or macrophages and a loss of rhythmicity through reproductive cycles. These data reveal a key role for monocytes and their progeny in the regulation of uterine tissue homeostasis.
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BibTeX
@article{shahzad2026dual,
title = {{The dual roles of uterine monocytes in regulation of tissue homeostasis throughout reproductive cycles in health and disease}},
author = {Abdullah Shahzad and Olivia Moran and Yousef Alebrahim and Stefano Colombo and Livia Lacerda Mariano and Olivia Shorthouse and Hannah Morgan and Daxina Bhatt and Nicholas Scott and Felicity Hunter and Catriona Laverty and Peter Ruane and Gerard Graham and Isabel Paterson and Navneet Kaur and Zohra Amin and Mariam Lokman and I-Hsuan Lin and Syed Murtuza-Baker and Michael Haley and Ian Donaldson and Jenny Myers and Daniel Brison and John Aplin and Molly Ingersoll and Laurence Pearmain and Lamiya Mohiyiddeen and Elizabeth Mann},
journal = {Nature Immunology},
year = {2026},
month = sep,
doi = {10.1038/s41590-026-02651-y},
url = {https://pasteur.hal.science/pasteur-05765219v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The dual roles of uterine monocytes in regulation of tissue homeostasis throughout reproductive cycles in health and disease
AU - Abdullah Shahzad
AU - Olivia Moran
AU - Yousef Alebrahim
AU - Stefano Colombo
AU - Livia Lacerda Mariano
AU - Olivia Shorthouse
AU - Hannah Morgan
AU - Daxina Bhatt
AU - Nicholas Scott
AU - Felicity Hunter
AU - Catriona Laverty
AU - Peter Ruane
AU - Gerard Graham
AU - Isabel Paterson
AU - Navneet Kaur
AU - Zohra Amin
AU - Mariam Lokman
AU - I-Hsuan Lin
AU - Syed Murtuza-Baker
AU - Michael Haley
AU - Ian Donaldson
AU - Jenny Myers
AU - Daniel Brison
AU - John Aplin
AU - Molly Ingersoll
AU - Laurence Pearmain
AU - Lamiya Mohiyiddeen
AU - Elizabeth Mann
PY - 2026
DA - 2026/09/08
JO - Nature Immunology
DO - 10.1038/s41590-026-02651-y
UR - https://pasteur.hal.science/pasteur-05765219v1
AB - Inflammation occurs during the recurring cycles of tissue degradation, repair and remodeling in the uterus, but the mechanisms by which the immune system contributes to uterine tissue integrity are unclear. We reveal that uterine monocytes have dual roles in both tissue remodeling and inflammation, depending on the reproductive cycle stage. Circulating inflammatory monocytes infiltrated the uterus before their differentiation into proinflammatory or pro-repair macrophages, depending on interferon-γ and transforming growth factor-β, respectively. Human monocyte numbers peaked before the window of implantation, when an inflammatory environment is required for embryo implantation. Uterine monocytes exhibited cytotoxic properties, regulating epithelial cell apoptosis. Bioinformatic analyses of receptor–ligand interactions indicated that monocytes dominated interactions between myeloid cells and fibroblasts. These pathways were disrupted in uterine fibrosis, marked by excess inflammatory monocytes or macrophages and a loss of rhythmicity through reproductive cycles. These data reveal a key role for monocytes and their progeny in the regulation of uterine tissue homeostasis.
SN - 1529-2908
SN - 1529-2916
ER -