| First Author | Barilla RM | Year | 2025 |
| Journal | Science | Volume | 389 |
| Issue | 6757 | Pages | 260-267 |
| PubMed ID | 40403128 | Mgi Jnum | J:367693 |
| Mgi Id | MGI:8207521 | Doi | 10.1126/science.adn9850 |
| Citation | Barilla RM, et al. (2025) Type 2 cytokines act on enteric sensory neurons to regulate neuropeptide-driven host defense. Science :eadn9850 |
| abstractText | 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 beta (CGRPbeta) and coexpressing receptors for the type 2 cytokines interleukin-4 (IL-4) and IL-13. Type 2 cytokines amplified NMU and CGRPbeta 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 CGRPbeta rescued helminth clearance deficits and restored anti-helminth immunity, highlighting the essential bi-directional neuro-immune crosstalk regulating intestinal type 2 inflammation. |
