Intestinal epithelial autophagy protects from cytokine-driven mortality and IFNγ-dependent cell death in acute small intestinal injury
Bibliographic record
Abstract
Abstract Crohn’s disease (CD) is characterized by a breakdown of the intestinal mucosal barrier. A genetic polymorphism of the autophagy gene ATG16L1 is associated with increased risk of developing CD, and it impairs the protective and regenerative functions of the intestinal epithelium. Autophagy acts as a regulator of cell death and has been implicated in the protection from both necroptosis and apoptosis in the epithelium. Our work showed that mice specifically deleted for Atg16l1 in intestinal epithelial cells (Atg16l1ΔIEC) had exacerbated T cell-mediated intestinal damage in the model of anti-CD3 enteropathy compared to wild-type mice, which was characterized by crypt epithelial cell death and heightened inflammation. Moreover, Atg16l1 deficiency delayed the recovery of the intestinal epithelium, and Atg16l1-deficient IECs were impaired in their proliferative response. Pathology and mortality were largely driven by microbiota-dependent expression of Ifng, Tnf, and type I IFN response genes in Atg16l1ΔIEC mice. Mechanistically, while survival was rescued by blocking these cytokine pathways independently, only anti-IFNγ treatment abrogated intestinal epithelial cell (IEC) death in Atg16l1ΔIEC mice, thereby decoupling IEC death and survival. In summary, our findings suggest differential roles for IFNγ, TNF, and type I IFN in acute enteropathy and IEC death in the context of autophagy deficiency. Supported by grants from CIHR (MOP-12353, FDN-14333) and NSERC (RGPIN-201).
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 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) | 0.001 | 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".