Dedicated macrophages organize and maintain the enteric nervous system

Area of Science:

• Neuroscience
• Immunology
• Gastroenterology

Background:

• The enteric nervous system (ENS) is critical for gut function but immature at birth.
• Postnatal development requires significant refinement of the ENS for adult physiological roles.

Purpose of the Study:

• To investigate the role of muscularis externa macrophages (MMϕ) in ENS development and maintenance.
• To elucidate the reciprocal communication between MMϕ and the ENS.

Main Methods:

• Macrophage depletion experiments before weaning.
• Analysis of intestinal transit and enteric neuron populations.
• Investigation of transforming growth factor-β signaling pathways.

Main Results:

• MMϕ prune synapses and phagocytose enteric neurons during early life, refining the ENS.
• Depletion of MMϕ leads to abnormal intestinal transit.
• Post-weaning, MMϕ adopt a neurosupportive role, influenced by ENS-derived TGF-β.
• Disruption of ENS-TGF-β signaling alters MMϕ phenotype and leads to enteric neuron loss.

Conclusions:

• Resident MMϕ play a dual role in ENS development and maintenance, adapting their function over time.
• A reciprocal communication axis exists between the ENS and MMϕ, essential for gut homeostasis.
• The ENS, like the brain, is shaped and maintained by specialized resident macrophages.