Disrupting the TRAF1/cIAP2 interaction attenuates inflammasome activation and protects against monosodium urate crystal–induced arthritis
Bibliographic record
Abstract
Tumor necrosis factor receptor (TNFR)-associated factor 1 (TRAF1) regulates NF-κB signaling and is implicated in chronic autoimmune diseases characterized by persistent inflammation. In addition to its role in restraining linear ubiquitin assembly complex-mediated linear ubiquitination of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) to limit inflammasome activation, TRAF1 also stabilizes cellular inhibitor of apoptosis protein 2 (cIAP2) by protecting it from degradation. Notably, cIAP2 promotes inflammasome activation via K63-linked polyubiquitination of caspase-1. Here, we show that disrupting the TRAF1/cIAP2 interaction (V203A in humans; V196A in mice) reduces inflammasome activation. TRAF1V203A THP-1 cells exhibit diminished caspase-1 ubiquitination, leading to impaired IL-1β secretion. Similarly, TRAF1V196A mice produce significantly lower IL-1β levels after LPS challenge. In a monosodium urate crystal-induced arthritis model, TRAF1V196A mice show reduced joint inflammation, decreased synovial immune cell infiltration, and attenuated disease severity. These findings establish the TRAF1/cIAP2 axis as a key regulator of inflammasome activation and a potential therapeutic target for inflammasome-driven diseases such as gout.
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 distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".