Viola, MF;
Chavero-Pieres, M;
Modave, E;
Delfini, M;
Stakenborg, N;
Estévez, MC;
Fabre, N;
... Boeckxstaens, G; + view all
(2023)
Dedicated macrophages organize and maintain the enteric nervous system.
Nature
, 618
(7966)
pp. 818-826.
10.1038/s41586-023-06200-7.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Dedicated macrophages organize and maintain the enteric nervous system |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41586-023-06200-7 |
| Publisher version: | https://doi.org/10.1038/s41586-023-06200-7 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Enteric Nervous System, Intestines, Lymphotoxin-alpha, Macrophages, Neurons, Weaning, Cell Communication, Transcriptome, Phenotype, Phagocytosis, Synapses, Neuronal Plasticity, Gastrointestinal Transit |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > UK Dementia Research Institute |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10173394 |
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