Increased susceptibility to colitis in the Vasoactive Intestinal Peptide receptor type 2 (VPAC2) mouse : A negative role for VPAC1 receptor in the induction of intestinal inflammation (50.44)
Bibliographic record
Abstract
Abstract Vasoactive intestinal peptide (VIP) is a prominent neuropeptide with effects on many immune functions which are transduced by VIP G-protein-coupled receptors type 1 (VPAC1) and type 2 (VPAC2) on immune cells. Previous studies have shown that VIP reduces clinical symptoms and inflammation in mouse models of human immune-based diseases such as rheumatoid arthritis, Crohn’s Disease, septic shock and multiple sclerosis. We recently demonstrated that VPAC2 knockout (KO) CD4 T cells in the presence of VIP and TGF-b develop into Th17 cells in a cAMP-Protein Kinase A dependent manner. Here we show that increased IL-17 induction in VPAC2-KO CD4 cells is accompanied by a reduced conversion of CD4 T cells into FoxP3+ regulatory T cells. To determine if VPACs play a role in the inflammatory bowel disease (IBD), VPAC2-KO mice were subjected to dextran sulfate sodium (DSS) in drinking water. Compared to wild type (WT), VPAC2-KO mice exhibited rapid and more severe clinical symptoms of colitis and had significantly higher colonic inflammation and increased inflammatory cytokines in colon. Severe colitis in VPAC2-KO mice was ameliorated in the presence of PKA inhibitors. Moreover, VPAC1-KO mice were resistant to the development of DSS-induced colitis. The results demonstrate a new role for VPAC1 which is responsible for increased inflammation in IBD and may provide a new therapeutic target.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".