CCR2+ Monocyte Depletion as Restoration of CNS Immune Privilege
Curated pathway from expert analysis
flowchart TD
A["CCL2/MCP-1 Gradient<br/>Blood-Brain Barrier Chemokine Field"]
B["CCR2+ Monocyte Recruitment<br/>Peripheral Immune Cell Extravasation"]
C["Microglial Activation Bias<br/>M1 Pro-inflammatory State Shift"]
D["Pro-inflammatory Cytokine Storm<br/>IL1B, TNF-alpha, IL6 Amplification"]
E["Synaptic Pruning Dysregulation<br/>Excess or Insufficient Phagocytosis"]
F["Neuronal Loss and Network Dysfunction<br/>Cognitive Decline Substrate"]
A --> B
B --> C
C --> D
D --> E
E --> F
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style D fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style F fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9aNo linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for CCL2 yet. Search RCSB →
Median TPM across 13 brain regions for CCL2/CCR2 axis; specifically CCR2+ monocytes 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 CCL2.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF CCR2+ monocytes are selectively depleted using CCR2-DTR bone marrow chimeric mice before EAE induction (via DT administration at 10 μg/g for 3 consecutive days), THEN clinical EAE scores will decre | EAE clinical score reduction of ≥40% and CNS CD45+ cell count reduction of ≥50% | — no observation — | pending | 0.65 |
| IF anti-CCR2 monoclonal antibody (clone MC-21) is administered at 10 mg/kg every 3 days for 4 weeks starting at EAE onset (score 1.0), THEN serum neurofilament light chain (NfL) concentrations will de | ≥35% reduction in serum NfL and ≥40% reduction in spinal cord MRI lesion volume | — no observation — | pending | 0.55 |