STAT3 Epigenetic Priming as Mechanism of Peripheral Cytokine Memory
Curated pathway from expert analysis
flowchart TD
A["Peripheral Cytokine<br/>IL-6 Elevation"]
B["Monocyte STAT3<br/>Phosphorylation Activation"]
C["Epigenetic Priming<br/>BRD4 Reader Complex"]
D["Pro-inflammatory Memory<br/>Training"]
E["Brain Border Macrophage<br/>Reprogramming"]
F["Neuroinflammation<br/>Amplification"]
G["IL-6/STAT3/BRD4 Axis<br/>as Immunomodulation Target"]
A --> B
B --> C
C --> D
D --> E
E --> F
G -.->|"modulates"| B
style A fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style F fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style G fill:#1b5e20,stroke:#a5d6a7,color:#a5d6a7No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for IL-6 yet. Search RCSB →
Median TPM across 13 brain regions for IL-6/STAT3/BRD4 axis; target: microglial STAT3 phosphorylation from GTEx v10.
No clinical trials data linked to this hypothesis yet.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for IL-6.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF BRD4 inhibitor JQ1 (50 mg/kg, intraperitoneally) is administered concurrently during peripheral IL-6 priming (100 ng/kg for 5 days), THEN the magnitude of microglial STAT3 phosphorylation elevation | Concurrent BRD4 inhibition will completely abolish the peripheral IL-6-induced priming of microglial STAT3 phosphorylation, reducing p-STAT3 to baseline levels | — no observation — | pending | 0.55 |
| IF adult C57BL/6 mice receive peripheral IL-6 administration (100 ng/kg, intraperitoneally) for 5 consecutive days, THEN isolated brain microglia will show significantly elevated STAT3 phosphorylation | Microglial p-STAT3 levels will remain elevated (≥2-fold above baseline) at 30 days post-IL-6 exposure, demonstrating persistent 'cytokine memory' effect. | — no observation — | pending | 0.65 |