通过空间转录组学研究雄激素性脱发中的免疫微环境紊乱。
Disturbance of Immune Microenvironment in Androgenetic Alopecia through Spatial Transcriptomics.
机构信息
Division of Dermatology, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani 12120, Thailand.
Chulabhorn International College of Medicine, Thammasat University, Pathum Thani 12120, Thailand.
出版信息
Int J Mol Sci. 2024 Aug 20;25(16):9031. doi: 10.3390/ijms25169031.
Androgenetic alopecia (AGA) is characterized by microinflammation and abnormal immune responses, particularly in the upper segment of hair follicles (HFs). However, the precise patterns of immune dysregulation remain unclear, partly due to limitations in current analysis techniques to preserve tissue architecture. The infundibulum, a major part of the upper segment of HFs, is associated with significant clusters of immune cells. In this study, we investigated immune cells around the infundibulum, referred to as peri-infundibular immune infiltration (PII). We employed spatial transcriptome profiling, a high-throughput analysis technology, to investigate the immunological disruptions within the PII region. Our comprehensive analysis included an evaluation of overall immune infiltrates, gene set enrichment analysis (GSEA), cellular deconvolution, differential expression analysis, over-representation analysis, protein-protein interaction (PPI) networks, and upstream regulator analysis to identify cell types and molecular dysregulation in immune cells. Our results demonstrated significant differences in immune signatures between the PII of AGA patients (PII-A) and the PII of control donors (PII-C). Specifically, PII-A exhibited an enrichment of CD4 helper T cells, distinct immune response patterns, and a bias toward a T helper (Th) 2 response. Immunohistochemistry revealed disruptions in T cell subpopulations, with more CD4 T cells displaying an elevated Th2 response and a reduced Th1-cytotoxic response compared to PII-C. These findings reveal the unique immune landscapes of PII-A and PII-C, suggesting potential for the development of innovative treatment approaches.
男性型脱发(AGA)的特征是微炎症和异常的免疫反应,特别是在毛囊的上段。然而,确切的免疫失调模式仍不清楚,部分原因是目前的分析技术在保留组织结构方面存在局限性。漏斗部是毛囊上段的主要部分,与大量免疫细胞簇有关。在这项研究中,我们研究了围绕漏斗部的免疫细胞,称为漏斗部周围免疫浸润(PII)。我们采用了空间转录组分析技术,这是一种高通量分析技术,来研究 PII 区域内的免疫失调。我们的综合分析包括评估整体免疫浸润、基因集富集分析(GSEA)、细胞去卷积、差异表达分析、过表达分析、蛋白质-蛋白质相互作用(PPI)网络和上游调节剂分析,以识别免疫细胞中的细胞类型和分子失调。我们的结果表明,AGA 患者的 PII(PII-A)和对照供体的 PII(PII-C)之间的免疫特征存在显著差异。具体而言,PII-A 表现出 CD4 辅助 T 细胞的富集、独特的免疫反应模式以及向 Th2 反应的偏向。免疫组织化学显示 T 细胞亚群的破坏,与 PII-C 相比,更多的 CD4 T 细胞表现出升高的 Th2 反应和降低的 Th1-细胞毒性反应。这些发现揭示了 PII-A 和 PII-C 的独特免疫景观,表明有可能开发创新的治疗方法。