Zhang Fei, Ge Qintao, Meng Jialin, Chen Jia, Liang Chaozhao, Zhang Meng
Department of Urology, The First Affiliated Hospital of Anhui Medical University; Institute of Urology, Anhui Medical University; Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, 230022, People's Republic of China.
Immunotargets Ther. 2024 Feb 26;13:111-121. doi: 10.2147/ITT.S451199. eCollection 2024.
The specific involvement of the CD8+ T effector memory RA (TEMRA) subset in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) has largely not been explored in the literature.
Targeted single-cell RNA sequencing (scRNA-seq) profiles were generated from peripheral blood mononuclear cells (PBMCs) obtained from two CP/CPPS patients and two healthy controls (HCs) in our recent study. Pseudotime series algorithms were used to reveal the differentiation trajectory, CellChat analysis was used to explore the communication between individual cells, and the SCENIC program was used to identify potential transcription factors (TFs). Based on the cosine similarity, clusters of differentially expressed genes (DEGs) were considered to be further enriched in different pathways. To confirm the functional role of the critical clusters, flow cytometry was employed.
The results revealed the molecular landscape of these clusters, with TEMRA cells exhibiting pronounced cytokine-mediated signaling pathway enrichment. Pseudotime trajectory analysis further mapped the evolution from naïve T cells to that of TEMRA cells, elucidating the developmental pathways involved in the immune context. A significant finding from CellChat analysis was the differential expression of ligands and receptors, with CD8+ TEMRA cells showing enhanced signaling, particularly in the CP/CPPS context, compared to HCs. Flow cytometry confirmed these results, revealing a heightened proinflammatory cytokine profile in patients with chronic prostatitis-like symptoms (CP-LS), suggesting that TEMRA cells play a significant role in disease pathogenesis. TF profiling across the T-cell clusters identified key regulators of cellular identity, identifying novel therapeutic targets. Elevated TNF signaling activity in CD8+ TEMRA cells underscored the involvement of these cells in disease mechanisms.
This study elucidates the pivotal role of the CD8+ TEMRA cell subset in CP/CPPS, which is characterized by increased TNF signaling and proinflammatory factor expression, highlighting potential biomarkers and opening new avenues for therapeutic intervention.
慢性前列腺炎/慢性盆腔疼痛综合征（CP/CPPS）患者中CD8 + 效应记忆RA（TEMRA）亚群的具体参与情况在很大程度上尚未在文献中得到探讨。
在我们最近的研究中，从两名CP/CPPS患者和两名健康对照（HC）获得的外周血单个核细胞（PBMC）生成靶向单细胞RNA测序（scRNA-seq）图谱。使用伪时间序列算法揭示分化轨迹，使用CellChat分析探索单个细胞之间的通信，并使用SCENIC程序识别潜在的转录因子（TF）。基于余弦相似度，差异表达基因（DEG）簇被认为在不同途径中进一步富集。为了确认关键簇的功能作用，采用了流式细胞术。
结果揭示了这些簇的分子景观，TEMRA细胞表现出明显的细胞因子介导的信号通路富集。伪时间轨迹分析进一步描绘了从初始T细胞到TEMRA细胞的进化过程，阐明了免疫背景中涉及的发育途径。CellChat分析的一个重要发现是配体和受体的差异表达，与HC相比，CD8 + TEMRA细胞显示出增强的信号传导，特别是在CP/CPPS背景下。流式细胞术证实了这些结果，揭示了慢性前列腺炎样症状（CP-LS）患者中促炎细胞因子谱升高，表明TEMRA细胞在疾病发病机制中起重要作用。跨T细胞簇的TF分析确定了细胞身份的关键调节因子，确定了新的治疗靶点。CD8 + TEMRA细胞中TNF信号活性升高强调了这些细胞参与疾病机制。
本研究阐明了CD8 + TEMRA细胞亚群在CP/CPPS中的关键作用，其特征是TNF信号传导和促炎因子表达增加，突出了潜在的生物标志物并为治疗干预开辟了新途径。
