Objective:

To explore the potential association of CCR1 with pSS immunopathology and to computationally assess its candidacy as a predicted target of Polygonatum odoratum.

Approach:

• Transcriptomic Analysis: Utilized transcriptomic datasets (GSE51092, GSE66795) and single-cell RNA sequencing data (GSE253568) from GEO to assess CCR1 expression.
• Network Pharmacology: Screened active component targets of P. odoratum and identified candidate therapeutic targets using a 'three-dimensional intersection' strategy.
• Single-Cell Analysis: Performed monocyte subtyping, pseudotime trajectory, SCENIC transcription factor network, and CellChat cell communication analyses.
• Molecular Docking: Predicted drug-target binding affinity of P. odoratum components to CCR1.
• RT-qPCR Validation: Validated findings in clinical samples from pSS patients (n = 65) and healthy controls (n = 48).

Key Findings:

• CCR1 was significantly upregulated in pSS patients (AUC = 0.758) and positively correlated with serum IgG levels (R = 0.49, P = 0.0057).
• Single-cell analysis showed CCR1 was highly expressed in classical monocytes, with CCR1-positive monocytes expanded in pSS (P = 0.0079).
• SCENIC analysis predicted STAT1 and EGR1 as upstream transcription factors associated with CCR1 expression.
• Moupinamide from P. odoratum showed predicted binding affinity with CCR1.

Interpretation:

The study provides exploratory evidence for CCR1's role in pSS immunopathology, particularly in monocyte recruitment and differentiation.

Limitations:

• The findings require experimental validation to confirm the computational predictions.
• The study is based on publicly available datasets, which may have inherent limitations.

Conclusion:

This study suggests CCR1 as a candidate therapeutic target in pSS, warranting further investigation into treatment strategies involving P. odoratum.