Elucidating the Role of Leucine-Rich Repeat Kinase 2 in Crohn’s Disease Pathogenesis and Neutrophil Biology
Bibliographic record
Abstract
Crohn’s disease (CD) is a debilitating chronic inflammatory bowel disease that can significantly reduce a person’s quality of life. Kinase domain gain-of-function variants of leucine-rich repeat kinase 2 (LRRK2), such as G2019S, are associated with an increased risk of CD and have been shown to enhance both myeloid cell trafficking and protection against intracellular infections, yet their role in disease pathogenesis remains elusive. Thus, we tested the hypothesis that LRRK2 kinase hyperactivity boosts enteric pathogen clearance in a selectively advantageous manner but simultaneously underlies the exacerbated inflammatory pathology characteristic of CD. We demonstrated that, in the context of C. rodentium-induced colitis, Lrrk2G2019S mice exhibited neither enhanced protection nor hyperinflammation relative to wild-type controls, and that neither the deficiency of Lrrk2 nor its G2019S mutation altered neutrophils’ capacity to degranulate in vitro or migrate in vivo. Future studies will aim to further investigate the role of LRRK2 in neutrophils using other models of inflammation.
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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 | 0.001 |
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".