Sensory neurons shape local macrophage identity via TGF-β signaling
Year: 2025
Type: article
Abstract: Resident macrophages play integral roles in maintaining tissue homeostasis and function. In the skin, prenatally seeded, specialized macrophages patrol sensory nerves and contribute to their regeneration after injury. However, mechanisms underlying the long-lasting postnatal commitment of these nerve-associated macrophages remain largely elusive. Here, we found that traumatic injury induced recruitment of myeloid progenitor cells to the sprouting axons of sensory nerves, where they gradually acquired a nerve-associated macrophage-like profile. This identity change was driven and maintained by the immediate microenvironment, particularly by transforming growth factor-β (TGF-β), which was locally activated by the physical interaction with nerves and integrin-mediated cleavage, and by the neuropeptide calcitonin gene-related peptide (CGRP). Moreover, TGF-β-mediated macrophage specification was essential for proper nerve regeneration following injury. Overall, we identify TGF-β as a conserved, spatially regulated mediator governing local imprinting and long-term specialization of macrophages within the subtissular neuronal niche, offering insights into precise bidirectional neuro-immune crosstalk underlying skin homeostasis.
Source: Immunity
Authors: Julia Kolter, Clarissa-Laura Döring, Samah Sarout, Sebastian Baasch, Lloyd Steele, Reem Alsumati, Gabriel V. Lucena Silva, Conceição E. Aníbal Silva, Isadora Marques Paiva, Zohreh Mansoori Moghadam, Vitka Gres, Florens Lohrmann, Philipp Aktories, Theresa Buchegger, Mitchell Bijnen, Layal Doumard, Benjamin Voisin, Christelle Le Foll, Nico Lachmann, Melanie Greter, Katrin Kierdorf, Muzlifah Haniffa, Thiago M. Cunha, Vincent Flacher, Philipp Henneke
Institutions: University of Freiburg, University Medical Center Freiburg, Wellcome Sanger Institute, Universidade de São Paulo, Medizinische Hochschule Hannover, University of Zurich, Centre National de la Recherche Scientifique, Immunologie, Immunopathologie et Chimie Thérapeutique, Institut de Biologie Moléculaire et Cellulaire, Université de Strasbourg, Fraunhofer Institute for Toxicology and Experimental Medicine, NIHR Newcastle Biomedical Research Centre, Newcastle University
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Funders: European Commission, Deutsche Forschungsgemeinschaft, Agence Nationale de la Recherche, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Deutsches Zentrum für Lungenforschung, Horizon 2020 Framework Programme, European Research Council, FP7 Coordination of Research Activities, H2020 European Research Council, H2020 Marie Skłodowska-Curie Actions
Awards: From iPSC-Macrophage Biology Towards Regenerative Therapies Targeting Respiratory Infections, Immunocompetence and vascularisation for a skin-on-a-chip model., G1284162446, G1425278750, G1605809255, G259924242, G2905232255, G314160780, G3492451836, Identification of markers for personal phenotyping in Acne Inversa, SFB 1479: Onkogengetriebener Immun Escape (OncoEscape), TRR 359: Perinatale Entwicklung der ImmunzellTopologie (PILOT), SFB 1160: Immunpathologie aufgrund eingeschränkter Immunreaktionen (IMPATH), EXC 2189: CIBSS Centre for Integrative Biological Signalling Studies, Astrocytes: a cornerstone in the control of food intake and energy homeostasis by hypothalamic fatty acid sensing neurons, TRR 167: Entwicklung, Funktion und Potential von myeloiden Zellen im zentralen Nervensystem (NeuroMac), G5931083012, Autophagy-mediated control of tissue-resident macrophage maintenance and function, G6411676481, G735672719, G7940440851, G7959360142, G7994596902
OpenAlex ID: W4414014116