Butyrophilin Btn3a2 connects Parp9/14 activation downstream of Xrn1 with XIAP/RIPK2 induction.
Bibliographic record
Abstract
We used a systems biological approach to deciphering mechanism with causative influence in human IBD based on factor identification upstream and downstream of NOD2. Parp9/14 were isolated as common-regulated targets in a transcriptomic discovery approach using multiple IBD-susceptibility genes including NOD2, TRIM22 and XIAP, which revealed Parp9/14 control of the butyrophilins Btn3a2. We demonstrate here that Btn3a2 is associated with a novel MHC class I program whose aligned expression in a network serves as the basis for a mechanism for recognition of self. This self non-self recognition mechanism is likely different from described mechanisms that utilize expression of lymphocyte (Ly) Rhesus (Rh), blood group and transplantation-associated antigens to indicate presence of non-self. Disturbed butyrophilin signaling by BTN3A2 retrieved TNFRSF14, the receptor for LIGHT, a molecule we recently demonstrated was a cardinal Crohn's Disease Montreal B3 phenotype (penetrating/fistulizing-type) susceptibility factor, and whose expression was the major component of a monocyte-macrophage lineage switch associated with transcriptional response to the pathogen-associated molecular pattern muramyl dipeptide (MDP). We demonstrate here a mechanism by which butyrophilin Btn3a2 connects Parp9/14 activation downstream of Xrn1 with XIAP/RIPK2 induction resulting in disease-specific induction of aggressive penetrating disease via TNFRSF14.
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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".