Dedicated macrophages organize and maintain the enteric nervous system.

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-β produced by the ENS; depletion of the ENS and disruption of transforming growth factor-β 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. © 2023. The Author(s), under exclusive licence to Springer Nature Limited.

Citation

Maria Francesca Viola, Marta Chavero-Pieres, Elodie Modave, Marcello Delfini, Nathalie Stakenborg, Maria Cuende Estévez, Naomi Fabre, Iris Appeltans, Tobie Martens, Katy Vandereyken, Hannah Theobald, Jens Van Herck, Philippe Petry, Simon Verheijden, Sebastiaan De Schepper, Alejandro Sifrim, Zhaoyuan Liu, Florent Ginhoux, Mohamad Azhar, Andreas Schlitzer, Gianluca Matteoli, Katrin Kierdorf, Marco Prinz, Pieter Vanden Berghe, Thierry Voet, Guy Boeckxstaens. Dedicated macrophages organize and maintain the enteric nervous system. Nature. 2023 Jun;618(7966):818-826

Mesh Tags

Substances

PMID: 37316669

search → result