Loss of colonic epithelial NCOR1 aggravates experimental colitis chronicity
Bibliographic record
Abstract
The nuclear co‐repressor NCOR1 orchestrates the assembly of a large transcriptional repression complex that is involved in the negative regulation of pro‐inflammatory genes. Chronic intestinal inflammation is associated with sustained activation of pro‐inflammatory molecules. Since NCOR1 is considered as a potent repressor of pro‐inflammatory genes in macrophages, we aimed to investigate the role of intestinal epithelial NCOR1 during inflammatory stresses. Conditional deletion of Ncor1 in the whole intestinal epithelium was achieved by crossing Villin‐Cre and Ncor1 loxP/loxP C57BL/6 mouse models. DSS‐induced colitis in NCOR1 Δ IEC mice was more severe than control mice according to survival as well as clinical observations. A gene profiling analysis in the colon of non‐diseased NCOR1 Δ IEC and control mice identified 85 unique and mapped transcripts being significantly modulated between NCOR1 Δ IEC and control mice. An Ingenuity Pathway Analysis from these predicted target genes identified gastrointestinal disease (79 transcripts) as top disease and biofunction. Analysis of enriched targets in specific canonical pathways predicted an increase in the tryptophan degradation pathway ( P = 3.2E‐02), a pathway recently demonstrated to be strongly relevant to inflammatory bowel disease severity. Indoleamine‐pyrrole 2,3‐dioxygenase (IDO1), that catalyzes the first and rate‐limiting step of tryptophan oxidation, was induced more than 7 times in the colon of NCOR1 Δ IEC mice. IDO1 was also significantly more elevated in NCOR1 Δ IEC mice when compared to control mice both subjected to chronic inflammation (3 cycles of DSS). Spontaneous induction of Ido1 gene expression was also confirmed in cultured ex vivo colon organoids deleted for Ncor1 . In conclusion, our results highlight the critical role of NCOR1 to maintain intestinal inflammatory homeostasis during experimental colitis and uncover a novel function for NCOR1 in the regulation of Ido1 expression and potentially tryptophan metabolism. Support or Funding Information Canadian Institutes of Health Research
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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) | 0.002 | 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 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".