Synovial lining macrophages form during early postnatal life via fetal-derived CX3CR1+ cells and AQP1+ intermediates
Year: 2026
Type: article
Abstract: Summary Synovial joints harbor a protective lining layer, consisting of fibroblasts and macrophages, which form an epithelial-like barrier. In inflamed joints, lining macrophages regulate both early inflammatory cell influx and resolution. Despite these critical functions, it is currently unknown at what stage during development the synovial macrophage lining is established, and which signals drive this process. Here, we use a combination of genetic models and in vivo perturbations, single cell transcriptomics and imaging to delineate the process of lining formation in mice. We find that the synovial lining is immature at birth and becomes established within the first 3 weeks of life. In this window, the lining is gradually populated with macrophages that originate from fetal sources, proliferate and acquire the lining-specific transcriptional identity. In contrast, monocytes contribute only minimally to the developing lining, and their input remains limited in healthy adulthood. We identify CSF1 and TGFβ as key signals in this process, which also involves mechanosensing through PIEZO1. Our study thus identifies the early postnatal window as a critical period for lining macrophage development, with potential lifelong impact on joint health and disease.
Source: Cell Reports
Authors: Marlene Magalhaes Pinto, Bert Malengier-Devlies, Guillaume Seuzaret, Anna Ahlback, Solvig Becker, Katelyn Patatsos, Georgios Drakoulis, Julia Karjalainen, Christiane Ruedl, David Voehringer, Calum C Bain, Elaine Emmerson, Barbora Schonfeldova, Kristina Zec, Irina Udalova, Theodoros Simakou, Lucy MacDonald, Mariola Kurowska-Stolarska, Jadwiga Zarebska, Tonia Vincent, Romeo Ricci, Eric Erbs, Jack Barrington, Barry W McColl, Georgiana Neag, Samuel Kemble, Christopher Mahony, Adam Croft, Louis Boon, Nicole Migotsky, Megan L Killian, Oumaima Ben Brahim, Stefan Uderhardt, Alexandre Gallerand, Stoyan Ivanov, Rebecca Gentek
Institutions: University of Edinburgh, University of Glasgow, University of Oxford, National University of Singapore, Friedrich-Alexander-Universität Erlangen-Nürnberg, Kennedy Institute of Rheumatology, Arthritis UK, Institut de génétique et de biologie moléculaire et cellulaire, University of Birmingham, University of Michigan, Universitätsklinikum Erlangen, Université Côte d'Azur, Centre National de la Recherche Scientifique, Laboratoire de PhysioMédecine Moléculaire
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: Wellcome Trust, Kennedy Trust for Rheumatology Research, Royal Society, University of Edinburgh, Deutsche Forschungsgemeinschaft, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Versus Arthritis, UK Dementia Research Institute, Medical Research Council, European Research Council, HORIZON EUROPE European Research Council
Awards: G1641517065, G168679249, Investigating the role of TGFβ in the functional imprinting of pulmonary macrophages in health and disease, Therapeutic role of CD44 in alcoholic liver diseases: from bone marrow myelopoiesis to liver inflammation, G2394575712, G2605610293, Dissecting the cellular and molecular basis of macrophage-nerve crosstalk in the salivary gland in health and regeneration, G339059223, G394222476, Metabolic control of IL-23 production in resident and migratory dendritic cells, G5728235598, G5857119584, Defining Brown Adipose Tissue Macrophage Diversity and Functions., Untersuchung gewebeprotektiver Funktionen von Makrophagen mittels integrativer und funktioneller Gewebebiologie., G7080048889, Network Synergies in Tissue Homeostasis and Stromal Prevention of Inflammatory Disease., Ether-Lipid Metabolism in Myeloid Cells in Atherosclerosis, G7333958791, G748436762, G7762209315, G8110842792, FOR 2886: PANDORA Pathways triggering AutoimmuNity and Defining Onset of early Rheumatoid Arthritis, TRR 369: DIONE Entzündungsbedingte Knochendegeneration, Investigating the role of TGFβ in the functional imprinting of pulmonary macrophages in health and disease
OpenAlex ID: W7203478805