Synovial lining macrophages form during early postnatal life via fetal-derived CX3CR1+ cells and AQP1+ intermediates

Magalhaes MS, Malengier-Devlies B, Seuzaret G, Ahlback A, Becker S, Patatsos K, Drakoulis G, Karjalainen J, Ruedl C, Vöhringer D, Bain CC, Emmerson E, Schonfeldova B, Zec K, Udalova I, Simakou T, MacDonald L, Kurowska-Stolarska M, Miotla-Zarebska J, Vincent T, Ricci R, Erbs E, Barrington J, McColl BW, Neag G, Mahony C, Croft AP, Boon L, Vermeren M, Bajénoff M, Ben Brahim O, Uderhardt S, Gallerand A, Ivanov S, Gentek R (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Cell Reports Elsevier (Cell Press)

Book Volume: 45

Article Number: 117698

Journal Issue: 8

DOI: 10.1016/j.celrep.2026.117698

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.

Authors with CRIS profile

David Vöhringer Department of Infection Biology Oumaima Ben Brahim Department of Medicine 3 – Rheumatology and Immunology Stefan Uderhardt Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

National University of Singapore (NUS) SG Singapore (SG) University of Birmingham GB United Kingdom (GB) University of Edinburgh GB United Kingdom (GB) University of Oxford GB United Kingdom (GB) University of Glasgow GB United Kingdom (GB) Institute of Genetics and Molecular and Cellular Biology / Institut de génétique et de biologie moléculaire et cellulaire (IGBMC) FR France (FR) JJP Biologics PL Poland (PL) Immunology Center of Marseille-Luminy FR France (FR) University of Côte d'Azur / Université Côte d'Azur FR France (FR)

How to cite

APA:

Magalhaes, M.S., Malengier-Devlies, B., Seuzaret, G., Ahlback, A., Becker, S., Patatsos, K.,... Gentek, R. (2026). Synovial lining macrophages form during early postnatal life via fetal-derived CX3CR1+ cells and AQP1+ intermediates. Cell Reports, 45(8). https://doi.org/10.1016/j.celrep.2026.117698

MLA:

Magalhaes, Marlène S., et al. "Synovial lining macrophages form during early postnatal life via fetal-derived CX3CR1+ cells and AQP1+ intermediates." Cell Reports 45.8 (2026).

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