Identification of Immune Microenvironment Changes, Immune-Related Pathways and Genes in Male Androgenetic Alopecia

Abstract

Although Androgenetic Alopecia (AGA) is classified as a non-inflammatory alopecia, histological evidence of microinflammation has long been recognized. However, the changes in the immune microenvironment, the immune-related pathway and the expression of Immune-related genes (IRGs) involved in AGA remain unclear. The microarray gene expression data (GSE36169) from patients with male AGA were analyzed. Gene Set Enrichment Analysis (GSEA) among statistically changed genes was done. KEGG and GO analyses among differentially expressed genes (DEGs) were performed. DEGs were screened to identify IRGs based on the ImmPort database. The cytohubba-MCC plugin of Cytoscape was applied to screen hub immune genes. The infiltration levels of 28 immune cells were quantified adopting single-sample GSEA (ssGSEA) algorithm. The microarray gene expression data (GSE90594) of male AGA was analyzed to validate hub IRGs genes and differential infiltrated immune cells. The ssGSEA revealed γδT cell, central memory CD8+ T cell, mast cell, immature B cell, activated CD8+ T cell, effector memory CD4+ T cell, eosinophil and neutrophil were significantly increased infiltration in the bald scalp. GSEA showed statistically changed genes were most enriched in immune related pathways, including innate immune system, adaptive immune system, cytokine signaling, interferon-γ signaling, interferon signaling and interleukins signaling. The four hub IRGs, including MMP9, PTPRC, BMP2 and THBS1, were enriched in the pathways of allograft rejection, coagulation and interferon-γ response. In summary, we proposed that the increase in γδ T cells, central memory CD8+ T cells, activated CD8+ T cell as well as the infiltration of mast cells contributed to immune microenvironment changes in male AGA. The 4 hub IRGs may be involved in the development and progression of hair loss in male AGA through interferon-γ signal pathways.