Human DcR3 overexpression in mice results in a systemic lupus erythematosus-like syndrome (129.15)
Bibliographic record
Abstract
Abstract OBJECTIVE: DcR3, a TNFR family member, is a secreted protein, and can enhance cell survival by interfering with multiply apoptosis pathways. The objective of this study was to understand the role of DcR3 in pathogenesis of autoimmune diseases. METHODS: We generated transgenic (Tg) mice with actin promoter-driven expression of human DcR3, and investigated the development of autoimmune diseases in these mice. RESULTS: Beyond 5–6 months of age, DcR3 Tg mice developed a systemic lupus erythematosus (SLE)-like syndrome. They produced autoantibodies against various organs, and against dsDNA and Smith Ag. The kidneys of these Tg mice showed pathological changes indicative of glomerular nephritis and IgG and C3 deposition; kidney dysfunctions, such as proteuria, leukocyturia, and hemuresis, were obvious. Aged Tg mice also developed skin lesions and lymphocyte infiltration in the liver, and suffered from leukopenia, anemia and thrombocytopenia. The SLE-like symdrome penetrance in DcR3 Tg mice was gender-dependent, with about 60% in females versus 20% in males. Mechanistically, exogenous recombinant DcR3 or endogenous DcR3 produced by Tg T cells effectively protected CD4 cells from activation-induced apoptosis in vitro. Probably as a consequence, in the peripheral blood of Tg mice beyond 6 months of age, CD4 cells with a phenotype of previous activation were increased. CONCLUSION: DcR3 overexpression could lead to a SLE-like syndrome in mice.
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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 | 0.001 |
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
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".