Synovial lining macrophages form during early postnatal life via fetal-derived CX3CR1+ cells and AQP1+ intermediates
Abstract
The synovial lining maintains joint integrity, produces lubricating fluid, and forms a sterile barrier disrupted in inflammatory joint disease. It consists of specialized fibroblasts and macrophages, but its developmental timing and mechanisms are not well understood. We used genetic mouse models, imaging, and single-cell transcriptomic profiling to delineate this process. We found that the lining is immature in fetal human and newborn mouse joints. In mice, fibroblasts provide full coverage at birth, whereas macrophages are scarce. The macrophage lining layer gradually forms during the first weeks of life in a colony-stimulating factor 1 (CSF1)-dependent process, largely monocyte-independent, involving fetal-derived Cx3cr1+ macrophages and Aqp1+ intermediates. Both lining macrophages and fibroblasts undergo substantial transcriptional changes postnatally, acquiring their specific identity, upregulating key genes such as Prg4 (fibroblasts) and Vsig4 (macrophages), and establishing active signaling units. Early postnatal life is therefore a critical window for synovial lining maturation with implications for joint health and disease.
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BibTeX
@article{magalhaes2026synovial,
title = {{Synovial lining macrophages form during early postnatal life via fetal-derived CX3CR1+ cells and AQP1+ intermediates}},
author = {Marlène Magalhaes and Bert Malengier-Devlies and Guillaume Seuzaret and Anna Ahlback and Solvig Becker and Katelyn Patatsos and Georgios Drakoulis and Julia Karjalainen and Christiane Ruedl and David Voehringer and Calum Bain and Elaine Emmerson and Barbora Schonfeldova and Kristina Zec and Irina Udalova and Theodoros Simakou and Lucy Macdonald and Mariola Kurowska-Stolarska and Jadwiga Miotla-Zarebska and Tonia Vincent and Romeo Ricci and Eric Erbs and Jack Barrington and Barry Mccoll and Georgiana Neag and Christopher Mahony and Adam Croft and Louis Boon and Matthieu Vermeren and Marc Bajénoff and Oumaima Ben Brahim and Stefan Uderhardt and Alexandre Gallerand and Stoyan Ivanov and Rebecca Gentek},
journal = {Cell Reports},
year = {2026},
month = aug,
doi = {10.1016/j.celrep.2026.117698},
url = {https://hal.science/hal-05795429v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Synovial lining macrophages form during early postnatal life via fetal-derived CX3CR1+ cells and AQP1+ intermediates
AU - Marlène Magalhaes
AU - Bert Malengier-Devlies
AU - Guillaume Seuzaret
AU - Anna Ahlback
AU - Solvig Becker
AU - Katelyn Patatsos
AU - Georgios Drakoulis
AU - Julia Karjalainen
AU - Christiane Ruedl
AU - David Voehringer
AU - Calum Bain
AU - Elaine Emmerson
AU - Barbora Schonfeldova
AU - Kristina Zec
AU - Irina Udalova
AU - Theodoros Simakou
AU - Lucy Macdonald
AU - Mariola Kurowska-Stolarska
AU - Jadwiga Miotla-Zarebska
AU - Tonia Vincent
AU - Romeo Ricci
AU - Eric Erbs
AU - Jack Barrington
AU - Barry Mccoll
AU - Georgiana Neag
AU - Christopher Mahony
AU - Adam Croft
AU - Louis Boon
AU - Matthieu Vermeren
AU - Marc Bajénoff
AU - Oumaima Ben Brahim
AU - Stefan Uderhardt
AU - Alexandre Gallerand
AU - Stoyan Ivanov
AU - Rebecca Gentek
PY - 2026
DA - 2026/08/14
JO - Cell Reports
DO - 10.1016/j.celrep.2026.117698
UR - https://hal.science/hal-05795429v1
AB - The synovial lining maintains joint integrity, produces lubricating fluid, and forms a sterile barrier disrupted in inflammatory joint disease. It consists of specialized fibroblasts and macrophages, but its developmental timing and mechanisms are not well understood. We used genetic mouse models, imaging, and single-cell transcriptomic profiling to delineate this process. We found that the lining is immature in fetal human and newborn mouse joints. In mice, fibroblasts provide full coverage at birth, whereas macrophages are scarce. The macrophage lining layer gradually forms during the first weeks of life in a colony-stimulating factor 1 (CSF1)-dependent process, largely monocyte-independent, involving fetal-derived Cx3cr1+ macrophages and Aqp1+ intermediates. Both lining macrophages and fibroblasts undergo substantial transcriptional changes postnatally, acquiring their specific identity, upregulating key genes such as Prg4 (fibroblasts) and Vsig4 (macrophages), and establishing active signaling units. Early postnatal life is therefore a critical window for synovial lining maturation with implications for joint health and disease.
SN - 2211-1247
SN - 2211-1247
ER -