TY  - JOUR
AU  - Barilla, Rocky M
AU  - Berard, Clara
AU  - Sun, Linyu
AU  - Sandhu, Sumiti
AU  - Zaghouani, Sarah
AU  - Iyer, Krishna S
AU  - Altun, Gizem
AU  - Su, Chien-Wen
AU  - Deguine, Jacques
AU  - Singh, Vasundhara
AU  - Hou, Yu
AU  - Kusumakar, Kanupriya
AU  - Rutlin, Michael L
AU  - Rao, Meenakshi
AU  - Zaghouani, Habib
AU  - Shi, Hai Ning
AU  - Xavier, Ramnik J
AU  - Kuchroo, Vijay K
TI  - Type 2 cytokines act on enteric sensory neurons to regulate neuropeptide-driven host defense.
JO  - Science
VL  - 389
IS  - 6757
SN  - 0036-8075
CY  - Washington, DC
PB  - American Association for the Advancement of Science
M1  - DKFZ-2025-01066
SP  - 260-267
PY  - 2025
N1  - 2025 Jul 17;389(6757):260-267
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:40403128
DO  - DOI:10.1126/science.adn9850
UR  - https://inrepo02.dkfz.de/record/301545
ER  -