A17 THE NEUROPEPTIDE VIP REGULATES INTESTINAL IMMUNITY THROUGH MODULATING THE ACTIVATION AND RECRUITMENT OF GROUP 3 INNATE LYMPHOID CELLS
Notice bibliographique
Résumé
Group 3 innate lymphoid cells (ILC3s) are a class of innate lymphocytes that are emerging as key players in regulating intestinal inflammation, immunity and homeostasis. Through the production of the cytokine IL-22, ILC3s can modulate the function of intestinal epithelial cells (IECs), helping to maintain the IEC barrier integrity and promoting host defense against bacterial pathogens (such as Citrobacter rodentium). Recently, a handful studies have shown that ILC3s can communicate with the nervous system in the gut where neurons and immune cells are enriched. It remains largely unexplored how this neuroimmune communication regulates the number and function of ILC3s in the gut. To understand how the neuropeptide - vasoactive intestinal peptide (VIP), controls the expansion and function of ILC3s thereby regulating intestinal immunity under baseline and infection conditions. Wildtype (WT), Vip-/- and Rag1-/- mice were used. ILC3s and dendritic cells were isolated from the intestinal lamina propria using percoll gradients. ILC3s migration towards VIP was measured by a chemotaxis assay. The number and function of ILC3s was assessed using FACS. IL-22, RegIII-β, and RegIII-γ production was quantified by qPCR and/or ELISA. WT and Vip-/- mice were infected with C. rodentium for 4–10 days, and their susceptibility to infection assessed by measuring body weight loss, bacterial counts, and histological changes. Recombinant VIP, IL-22 or retinoic acid (RA) was IP injected into Vip-/- mice, with the mice subsequently analyzed for their susceptibility to C. rodentium infection. ILC3s were also isolated from Rag1-/- mice and injected into Vip-/- mice by the IV route, followed by infection with C. rodentium. VIP induced ILC3s migration through the receptor VPAC2. VIP also promoted gut homing receptor CCR9 expression on intestinal ILC3s, by enhancing RA production by intestinal dendritic cells. The loss of VIP led to reduced activation and recruitment of intestinal ILC3 cells, less IL-22 production, and abnormal IEC barrier function. Accordingly, Vip-/- mice proved highly susceptible to C. rodentium infection, suffering dramatic body weight loss, increased pathogen colonization, and worsened intestinal damage. Notably, recombinant IL-22 adminstration was sufficient to rescue Vip-/- mice from C. rodentium infection. Moreover, treatment with RA or VIP, or adoptive transfer of ILC3 cells were all able to increase the intestinal production of IL-22 and protect Vip-/- mice from infection. Our results reveal a novel neuroimmune axis whereby the neuropeptide VIP controls the activation and recruitment of ILC3s in the gut, thereby playing a key role in promoting mucosal defense against intestinal pathogens. CCC, CIHRNSERC
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».