IL-4 gene transfer to the small bowel serosa leads to intestinal inflammation and smooth muscle hyperresponsiveness
Bibliographic record
Abstract
Intestinal mucosal inflammation can lead to altered function of the underlying smooth muscle, which becomes hyperreactive to most contractile stimuli. Through nematode parasite infection models, T helper type 2 (Th2) cytokines have been implicated in intestinal muscle dysfunction; however, the mechanisms involved and the relevance of these findings to other forms of intestinal inflammation are unclear. Through gene transfer, we explored whether the Th2 cytokine IL-4 can mediate changes in longitudinal muscle function in the context of an adenoviral infection. Following abdominal surgery on mice, control beta-galactosidase-encoding recombinant adenoviruses and IL-4-encoding adenoviruses were applied to the serosal surface of the jejunum, leading to infection of cells in the serosa and in the mesentery. Marker transgene expression lasted for 3 wk and was accompanied by the recruitment of macrophages, lymphocytes, and neutrophils into the peritoneal cavity and mild inflammation at the site of infection. IL-4 transgene expression led to a stronger inflammatory response characterized by tissue eosinophilia and increased numbers of peritoneal mast cells and plasma cells. Whereas control virus infection had no effect on intestinal muscle function, infection with the IL-4 virus led to significant jejunal muscle hypercontractility, evident by day 7 postinfection. This modulation of smooth muscle function was shown to be IL-4 specific, since the application of an IL-5-encoding adenovirus induced tissue eosinophilia but did not alter muscle function. These results highlight an important causal role for IL-4 in the pathological regulation of enteric smooth muscle function and identify a novel strategy for gene transfer to the intestine.
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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 | 0.001 |
| 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".