A55 INVESTIGATING THE ROLE OF ENDOGENOUS INTERLEUKIN-10 IN INTESTINAL EPITHELIAL CELLS AND HOMEOSTASIS
Bibliographic record
Abstract
Abstract Background IL-10 is appreciated for its potent anti-inflammatory effects on leukocytes in mucosal immunity. However, far less attention has been paid to the impact of IL-10 on epithelial cells, which make up the crucial barrier interface between the host mucosa and the external environment. Furthermore, most studies examine the effects of exogenous IL-10, disregarding the possible presence and function of autocrine or paracrine IL-10 in the epithelium. Aims Using ex vivo organoids we aimed to examine the small intestinal epithelium for IL-10 and dissect any role for endogenously produced cytokine. Methods We growed small intestinal organoids (enteroids) from crypts isolated from C57BL/6 mice (WT) and IL-10-gene knockout mice (IL-10KO). Cellular markers were characterized through qpCR, while IL-10 and IL-10 receptor localization was characterized though immunofluorescence. Results We discovered that cells in WT enteroids expressed IL-10 and IL-10R1 constitutively throughout development. Immunofluorescent staining revealed that IL-10 localizes to Paneth cells and appears to be secreted apically. Having established that IL-10 is secreted in enteroids, we compared enteroids from IL-10KO versus WT mice. IL-10KO enteroids developed to morphologically resemble WT enteroids; however, we detected an imbalance with lower secretory cell markers over absorptive cell types in the IL-10KO enteroids, measured as less mRNA for lysozyme, cryptdins and mucin-2. Addition of IL-10 to IL-10KO enteroids did not correct these defects, but did ameliorate the lineage balance by reducing absorptive cell lineage markers (sucrose isomaltase). IL-10R1 was localized on both apical and basolateral side of cell in enteroids. We suspect that epithelial-derived IL-10 likely acts on apical IL-10R, which may conduct a different response from basolateral receptor stimulation. Conclusions In conclusion, IL-10 is present in the small intestinal epithelium; more remains to be determined regarding the role this cytokine plays in gut development and homeostasis. Funding Agencies NSERC
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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) | 0.003 | 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".