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001     301545
005     20250729115225.0
024 7 _ |a 10.1126/science.adn9850
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100 1 _ |a Barilla, Rocky M
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245 _ _ |a Type 2 cytokines act on enteric sensory neurons to regulate neuropeptide-driven host defense.
260 _ _ |a Washington, DC
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|b American Association for the Advancement of Science
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500 _ _ |a 2025 Jul 17;389(6757):260-267
520 _ _ |a 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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700 1 _ |a Berard, Clara
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700 1 _ |a Sun, Linyu
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700 1 _ |a Sandhu, Sumiti
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700 1 _ |a Zaghouani, Sarah
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700 1 _ |a Iyer, Krishna S
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700 1 _ |a Altun, Gizem
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700 1 _ |a Su, Chien-Wen
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700 1 _ |a Deguine, Jacques
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700 1 _ |a Singh, Vasundhara
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700 1 _ |a Hou, Yu
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700 1 _ |a Kusumakar, Kanupriya
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700 1 _ |a Rutlin, Michael L
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700 1 _ |a Rao, Meenakshi
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700 1 _ |a Zaghouani, Habib
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700 1 _ |a Shi, Hai Ning
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700 1 _ |a Xavier, Ramnik J
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700 1 _ |a Kuchroo, Vijay K
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