Spatial transcriptome reveals disturbance of peri-infundibular immune infiltration in androgenetic alopecia

Abstract Peri-infundibular immune infiltration (PII) is a crucial cluster of immune cells associated with human hair follicles (HFs), with potential importance in HF-immune interactions. Androgenetic alopecia (AGA) is characterized by microinflammation and abnormal immune responses, especially in the PII region. However, the precise patterns of immune dysregulation remain unclear due to limitations in current analysis techniques preserving tissue architecture. Here, we utilized spatial transcriptome profiling, a high-throughput analysis technology, to investigate the immunological disturbances within the PII region. We evaluated overall immune infiltrates, conducted gene set enrichment analysis (GSEA), cellular deconvolution, differential expression analysis, over-representation analysis, protein-protein interaction (PPI) network, and upstream regulator analysis to identify cell types and molecular dysregulation in immune cells. Our results demonstrated significant differences in immune signature between the PII of AGA patients (PII-A) and the PII of control donors (PII-C). PII-A exhibited enrichment in CD4 + helper T cells, distinct immune response patterns, and a bias toward the T helper (Th) 2 response. Immunohistochemistry confirmed the disturbed T cell subpopulations, with increased CD4 + T cells displaying elevated Th2 response but reduced Th1-cytotoxic response compared to PII-C. These findings reveal the unique immune landscapes of PII-A and PII-C, suggesting possibilities for the development of innovative treatment approaches.