UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Dedicated macrophages organize and maintain the enteric nervous system

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. Green open access

[thumbnail of De Schepper_220203_EM_Manuscript_corrections31773.pdf]
Preview
Text
De Schepper_220203_EM_Manuscript_corrections31773.pdf - Accepted Version

Download (1MB) | Preview

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
Downloads since deposit
131Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item