A17 THE NEUROPEPTIDE VIP REGULATES INTESTINAL IMMUNITY THROUGH MODULATING THE ACTIVATION AND RECRUITMENT OF GROUP 3 INNATE LYMPHOID CELLS
Bibliographic record
Abstract
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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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".