P0010 PP IL‐4 EXPOSURE MODULATES EPITHELIAL BARRIER FUNCTION OF FETAL HUMAN INTESTINAL XENOGRAFTS IN VIVO.
Bibliographic record
Abstract
Introduction: Milk allergy is a leading cause of morbidity in young infants. Its etiology remains unclear, but increased permeability of the intestinal epithelium may be involved in its pathogenesis. Data on intestinal permeability in neonates are scarce. Human fetal intestinal xenografts have proved to be an interesting in vivo model system to study the physiology of late gestational stage intestine. Here, we examined baseline permeability of intestinal fetal xenografts and the effect of IL-4, a Th2 cytokine which is elevated in atopic individuals and known to modulate epithelial barrier function in animal models of food allergy and in cultured epithelial cell monolayers. Methods: Segments of human fetal small intestine (gestational age ~14wks) were transplanted sc into SCID mice. At 12 weeks post-transplantation, mice were injected twice (48 and 24hrs before sacrifice) with human recombinant IL-4 (0.3ml of 10ng/ml IL-4, ip). Xenografts were then mounted in Ussing chambers to measure short-circuit current (Isc), Na+-dependent glucose absorption (delta Isc glucose), conductance (G) and flux of the macromolecular probe, horseradish peroxidase (HRP) over 1hr. CD23 (low affinity IgE receptor) expression was also measured by immunofluorescence. Results: Xenograft tissues had relatively low but consistent values for Isc and G, and responded to glucose with an increase in Isc indicating good viability (Table). Permeability to macromolecules (HRP flux) was 17 times higher in xenograft tissue than in control adult ileum (Söderholm et al, unpublished). IL-4 did not alter Isc, G or glucose absorption. In contrast, the flux of intact HRP was dramatically increased in IL-4 treated xenografts. In addition, IL-4 induced the expression of CD23 on epithelial cells. Conclusion: Human fetal intestinal xenografts exhibited a very high baseline macromolecular permeability which was further enhanced by IL-4, independently of changes in the paracellular pathway. Excessive uptake of antigens together with microbial toxins from the gut lumen in the neonatal period may be involved in the induction of milk/food allergy. Our findings may also have relevance for more severe gastrointestinal conditions such as necrotizing enterocolitis and inflammatory bowel disease.
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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) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".