{"_":"CCR1-mediated monocyte chemotaxis in the immunopathology of primary Sjögren's syndrome: multi-omics integration analysis and computational target prioritization implicating .","i":["Polygonatum odoratum"]}
原发性干燥综合征（pSS）是一种慢性系统性自身免疫性疾病，目前尚无特异性病因治疗。一种传统滋阴中药用于治疗pSS，但其分子机制尚不清楚。本研究旨在探讨CCR1与pSS免疫病理之间的潜在关联，并通过计算评估其作为P. odoratum预测靶点的可能性。从GEO获取了转录组数据集（GSE51092、GSE66795；验证集：GSE84844）和单细胞RNA测序数据（GSE253568）。网络药理学筛选了P. odoratum的活性成分靶点，并通过“三维交集”策略识别候选治疗靶点。进行了单细胞分析，包括单核细胞亚型分型、拟时序轨迹分析、SCENIC转录因子网络分析和CellChat细胞通讯分析。分子对接预测了药物-靶点结合，RT-qPCR在临床样本中验证了研究发现（pSS n = 65，HC n = 48）。CCR1是唯一同时满足“药物可靶向、疾病相关、差异表达”条件的候选靶点。CCR1在pSS患者中显著上调（AUC = 0.758，提示中等判别能力），并与血清IgG水平呈正相关（R = 0.49，P = 0.0057）。单细胞分析表明CCR1在经典单核细胞（CD14++CD16-）中特异性高表达，CCR1阳性单核细胞在pSS中显著扩增（P = 0.0079）。SCENIC分析预测STAT1和EGR1为可能与CCR1表达相关的候选上游转录因子。CellChat分析预测了一条潜在的“T/NK细胞来源的CCL5-CCR1介导的单核细胞趋化募集”信号轴。P. odoratum中的Moupinamide显示出与CCR1的预测结合亲和力（-8.1 kcal/mol）。RT-qPCR证实pSS外周血单个核细胞中CCR1表达升高（P < 0.0001）。本研究提供了探索性多维证据，与CCR1在pSS免疫病理中的候选作用相一致。CCR1主要表达于经典单核细胞，预测与STAT1/EGR1调控活性相关，并通过CCL5-CCR1趋化轴在计算层面与单核细胞募集相关联。拟时序分析提示了与CCR1表达动态相关的单核细胞分化轨迹差异的计算推断，尚需实验验证。P. odoratum中的Moupinamide显示出与CCR1的预测结合亲和力，为“滋阴润燥”治疗原则提供了计算假说，有待实验验证。
Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease with no specific etiological treatment. , a traditional yin-nourishing herb, is used in treating pSS, but its molecular mechanism remains unclear. This study aimed to explore the potential association of CCR1 with pSS immunopathology and to computationally assess its candidacy as a predicted target of P. odoratum. Transcriptomic datasets (GSE51092, GSE66795; validation: GSE84844) and single-cell RNA sequencing data (GSE253568) were obtained from GEO. Network pharmacology screened active component targets of P. odoratum, and a "three-dimensional intersection" strategy identified candidate therapeutic targets. Single-cell analyses including monocyte subtyping, pseudotime trajectory, SCENIC transcription factor network, and CellChat cell communication analyses were performed. Molecular docking predicted drug-target binding, and RT-qPCR validated findings in clinical samples (pSS n = 65, HC n = 48). CCR1 was the only candidate target simultaneously satisfying "drug-targetable, disease-related, and differentially expressed" conditions. CCR1 was significantly upregulated in pSS patients (AUC = 0.758, indicating moderate discriminatory capacity) and positively correlated with serum IgG levels (R = 0.49, P = 0.0057). Single-cell analysis demonstrated CCR1 was specifically highly expressed in classical monocytes (CD14++CD16-), with CCR1-positive monocytes significantly expanded in pSS (P = 0.0079). SCENIC analysis predicted STAT1 and EGR1 as candidate upstream transcription factors potentially associated with CCR1 expression. CellChat analysis predicted a potential "T/NK cell-derived CCL5-CCR1-mediated monocyte chemotactic recruitment" signaling axis. Moupinamide from P. odoratum showed predicted binding affinity with CCR1 (-8.1 kcal/mol). RT-qPCR confirmed elevated CCR1 expression in pSS PBMCs (P < 0.0001). This study provides exploratory multi-dimensional evidence consistent with a candidate role of CCR1 in pSS immunopathology. CCR1 is predominantly expressed in classical monocytes, predicted to be associated with STAT1/EGR1 regulatory activity, and computationally linked to monocyte recruitment through the CCL5-CCR1 chemotactic axis. Pseudotime analysis suggested a computational inference of monocyte differentiation trajectory differences associated with CCR1 expression dynamics, requiring experimental validation. Moupinamide from P. odoratum shows predicted binding affinity to CCR1, offering a computational hypothesis for the "yin-nourishing and dryness-moistening" therapeutic principle that warrants experimental validation.
Jianbin Li, Yuzhen Gesang, Ning Tan, Renhe Li, Wei Liu. {"_":"CCR1-mediated monocyte chemotaxis in the immunopathology of primary Sjögren's syndrome: multi-omics integration analysis and computational target prioritization implicating .","i":["Polygonatum odoratum"]}. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1867098.
Jianbin Li, Yuzhen Gesang, Ning Tan, Renhe Li, Wei Liu (2026). {"_":"CCR1-mediated monocyte chemotaxis in the immunopathology of primary Sjögren's syndrome: multi-omics integration analysis and computational target prioritization implicating .","i":["Polygonatum odoratum"]}. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1867098
Jianbin Li, Yuzhen Gesang, Ning Tan, Renhe Li, Wei Liu. {"_":"CCR1-mediated monocyte chemotaxis in the immunopathology of primary Sjögren's syndrome: multi-omics integration analysis and computational target prioritization implicating .","i":["Polygonatum odoratum"]}[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1867098.
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