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Dedicated macrophages organize and maintain the enteric nervous system.
Viola, Maria Francesca; Chavero-Pieres, Marta; Modave, Elodie; Delfini, Marcello; Stakenborg, Nathalie; Estévez, Maria Cuende; Fabre, Naomi; Appeltans, Iris; Martens, Tobie; Vandereyken, Katy; Theobald, Hannah; Van Herck, Jens; Petry, Philippe; Verheijden, Simon; De Schepper, Sebastiaan; Sifrim, Alejandro; Liu, Zhaoyuan; Ginhoux, Florent; Azhar, Mohamad; Schlitzer, Andreas; Matteoli, Gianluca; Kierdorf, Katrin; Prinz, Marco; Vanden Berghe, Pieter; Voet, Thierry; Boeckxstaens, Guy.
Afiliación
  • Viola MF; Laboratory for Intestinal Neuro-Immune Interaction, Translational Research Center for Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium.
  • Chavero-Pieres M; Laboratory for Intestinal Neuro-Immune Interaction, Translational Research Center for Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium.
  • Modave E; Laboratory for Intestinal Neuro-Immune Interaction, Translational Research Center for Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium.
  • Delfini M; Laboratory for Intestinal Neuro-Immune Interaction, Translational Research Center for Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium.
  • Stakenborg N; Laboratory for Intestinal Neuro-Immune Interaction, Translational Research Center for Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium.
  • Estévez MC; Laboratory for Intestinal Neuro-Immune Interaction, Translational Research Center for Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium.
  • Fabre N; Laboratory for Intestinal Neuro-Immune Interaction, Translational Research Center for Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium.
  • Appeltans I; Laboratory for Intestinal Neuro-Immune Interaction, Translational Research Center for Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium.
  • Martens T; Laboratory for Enteric NeuroScience, Translational Research Center for Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium.
  • Vandereyken K; Laboratory of Reproductive Genomics, Department of Human Genetics, KU Leuven, Leuven, Belgium.
  • Theobald H; KU Leuven Institute for Single Cell Omics, KU Leuven, Leuven, Belgium.
  • Van Herck J; Quantitative Systems Biology, LIMES-Institute, University of Bonn, Bonn, Germany.
  • Petry P; Laboratory of Reproductive Genomics, Department of Human Genetics, KU Leuven, Leuven, Belgium.
  • Verheijden S; Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • De Schepper S; Faculty of Biology, University of Freiburg, Freiburg, Germany.
  • Sifrim A; Laboratory for Intestinal Neuro-Immune Interaction, Translational Research Center for Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium.
  • Liu Z; Janssen Research and Development, Janssen Pharmaceutica NV, Beerse, Belgium.
  • Ginhoux F; Laboratory for Intestinal Neuro-Immune Interaction, Translational Research Center for Gastrointestinal Disorders, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium.
  • Azhar M; UK Dementia Research Institute, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
  • Schlitzer A; KU Leuven Institute for Single Cell Omics, KU Leuven, Leuven, Belgium.
  • Matteoli G; Laboratory of Multi-Omic Integrative Bioinformatics, Department of Genetics, KU Leuven, Leuven, Belgium.
  • Kierdorf K; Leuven AI Institute, KU Leuven, Leuven, Belgium.
  • Prinz M; Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Vanden Berghe P; Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Voet T; Singapore Immunology Network, Agency for Science, Technology & Research, Singapore, Singapore.
  • Boeckxstaens G; Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore.
Nature ; 618(7966): 818-826, 2023 Jun.
Article en En | MEDLINE | ID: mdl-37316669
Correct development and maturation of the enteric nervous system (ENS) is critical for survival1. At birth, the ENS is immature and requires considerable refinement to exert its functions in adulthood2. Here we demonstrate that resident macrophages of the muscularis externa (MMϕ) refine the ENS early in life by pruning synapses and phagocytosing enteric neurons. Depletion of MMϕ before weaning disrupts this process and results in abnormal intestinal transit. After weaning, MMϕ continue to interact closely with the ENS and acquire a neurosupportive phenotype. The latter is instructed by transforming growth factor-ß produced by the ENS; depletion of the ENS and disruption of transforming growth factor-ß signalling result in a decrease in neuron-associated MMϕ associated with loss of enteric neurons and altered intestinal transit. These findings introduce a new reciprocal cell-cell communication responsible for maintenance of the ENS and indicate that the ENS, similarly to the brain, is shaped and maintained by a dedicated population of resident macrophages that adapts its phenotype and transcriptome to the timely needs of the ENS niche.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sistema Nervioso Entérico / Intestinos / Macrófagos Idioma: En Revista: Nature Año: 2023 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Reino Unido
Texto completo
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sistema Nervioso Entérico / Intestinos / Macrófagos Idioma: En Revista: Nature Año: 2023 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Reino Unido