Dissecting the role of endogenous epithelial IL-10 using a small intestinal organoid model
Bibliographic record
Abstract
Abstract IL-10 is widely appreciated as a potent anti-inflammatory cytokine, acting on leukocytes in mucosal immunity. 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 look into the effects of exogenous IL-10, disregarding the possible presence and function of endogenous IL-10 in the epithelium. Using ex vivo organoids we aimed to dissect any role for endogenous epithelial IL-10. We discovered that cells in small intestinal organoids (enteroids) derived from C57BL/6 mice produced IL-10 constitutively throughout development. IL-10 mRNA increased considerably on day 3, the time when enteroids begin “budding” to create crypt-like structures. In addition, a second IL-10 increase was detected at day 6 when enteroids are typically “mature”. Immunofluorescent staining for IL-10 on day 4 enteroids was localized to Paneth cells. As gut epithelial cells are constantly exposed to bacteria, we added LPS at the start of enteroid cultures and observed that IL-10 staining was significantly increased. To further investigate the role of endogenous IL-10, we grew enteroids from IL-10 gene knockout mice. IL-10 deficient enteroids develop to morphologically resemble wild-type enteroids. We are proceeding to examine any difference in permeability, cell lineages and apoptosis between the two enteroid genotypes. In conclusion, IL-10 is present in the developing small intestinal epithelium and while development is IL-10-independent, whether IL-10 impacts subcellular components is under investigation.
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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 | 0.001 |
| 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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".