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| Home > Publications database > Type 2 cytokines act on enteric sensory neurons to regulate neuropeptide-driven host defense. |
| Home > Publications database > Type 2 cytokines act on enteric sensory neurons to regulate neuropeptide-driven host defense. |
| Journal Article | DKFZ-2025-01066 |
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2025
American Association for the Advancement of Science
Washington, DC
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Please use a persistent id in citations: doi:10.1126/science.adn9850
Abstract: Enteric nervous system (ENS)-derived neuropeptides modulate immune cell function, yet our understanding of how inflammatory cues directly influence enteric neuron responses during infection is considerably lacking. Here, we characterized a primary enteric sensory neuron (PSN) subset producing the neuropeptides neuromedin U (NMU) and calcitonin gene-related peptide β (CGRPβ) and coexpressing receptors for the type 2 cytokines interleukin-4 (IL-4) and IL-13. Type 2 cytokines amplified NMU and CGRPβ expression in PSNs, in vitro and in vivo, which was abrogated by PSN-specific Il13ra1 deletion. Deletion of Il13ra1 in PSNs impaired host defense to the gastrointestinal helminth Heligmosomoides polygyrus and blunted muscularis immune responses. Co-administration of NMU23 and CGRPβ rescued helminth clearance deficits and restored anti-helminth immunity, highlighting the essential bi-directional neuro-immune crosstalk regulating intestinal type 2 inflammation.
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