Bibliographic record
Abstract
Crohn’s disease (CD) has a profound impact on the quality of life of individuals living with this disease. In 2021, an estimated 300,000 people in Canada alone were living with either CD or ulcerative colitis (UC). CD causes discontinuous inflammatory lesions that can occur throughout the gastrointestinal tract but are most commonly located in the terminal ileum and colon. A combination of factors is thought to cause progression to CD, stemming from both a genetic predisposition and environmental risk factors, which together alter intestinal homeostasis, microbiota composition, and intestinal immune function. How intestinal homeostasis ultimately breaks down and leads to disease is not fully understood. A common coding variant of the autophagy protein ATG16L1 has been associated with risk for developing CD. Here, we explored a role for ATG16L1 in intestinal epithelial cells during acute small intestinal injury as well as recovery. We found that in the absence of ATG16L1 T cell-mediated damage was greatly increased in the mouse small intestine, characterized by increased inflammation and cell death. Moreover, ATG16L1 deficiency slowed the recovery of the intestinal epithelium, and Atg16l1-deficient IECs had an impaired proliferative response. Our study further explored the role of pro-inflammatory signaling in the cell death we had observed in Atg16l1ΔIEC mice during acute enteropathy. We found that IFNγ was driving cell death and overall pathology in Atg16l1ΔIEC mice. In contrast, blocking neither TNF nor type I IFN signaling was able to rescue the phenotype. In addition, cytokine expression and, concomitantly, cell death depended on the presence of the intestinal microbiota. Altogether, the work outlined in this thesis demonstrates a role for autophagy in protecting the intestinal epithelium from T cell-mediated damage and cytokine-induced cell death. This sheds further light on how the CD-associated ATG16L1 risk allele contributes to the disruption of intestinal homeostasis and development of pathological intestinal lesions.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| 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".