The RNA virus sensor melanoma differentiation-associated protein 5 mitigates protection from Coxsackievirus B4 and type 1 diabetes in non-obese diabetic mice. (P5211)
Bibliographic record
Abstract
Abstract Type 1 diabetes is a pancreatic autoimmune disease affecting children and results from both genetic and environmental factors where coxsackievirus B4 (CB4) is the most associated pathogen. Genome-wide association studies have linked variants in MDA5, an RNA virus sensor, with T1D protection. As CB4 is an RNA virus and a likely factor in T1D etiology, we chose to use CB4 to study the role of MDA5 in T1D. CB4 infection enhances T1D in NODs through activation of autoreactive T cells. We hypothesized that MDA5 signals the strength, polarization and regulation of the T cell response after stimulation by agents like CB4 and dampening MDA5 function would alter the T cell response to favour T1D protection. MDA5ko(-/-) were backcrossed to the NOD background and confirmed by SNP analysis. NOD-MDA5ko(10/10) failed to develop spontaneous T1D by 24 weeks when T1D occurred in MDA5het(+/-)(2/10) and wt(+/+)(9/33). While decreased MDA5 expression (confirmed by Western) in MDA5het did not affect spontaneous T1D, it protected MDA5het(4/4) from CB4 induced T1D compared to infected wt(2/4). FACS analysis revealed significantly fewer activated effector CD4+ T cells in the spleen and PLNs of MDA5hets. Further, MDA5het PLNs had increased numbers of natural Tregs. These results support our premise that reduced MDA-5 expression alters the T cell response limiting the development of autoreactive effectors and T1D and suggests that dampening MDA-5 function could be a key therapeutic target.
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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) | 0.001 | 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 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".