Identification of Distinct Immune Signatures and Chemokine Networks in Scalp Inflammatory Diseases

Abstract Background Alopecia areata (AA), cutaneous lupus erythematosus (CLE), and psoriasis are diseases that often affect the scalp. AA and CLE often lead to hair loss, whereas psoriasis does not. The underlying mechanisms contributing to these differential prognoses remain unclear. Methods Microarray datasets of the three scalp diseases were collected from the GEO database and were integrated by sva R package. Differentially expressed genes (DEGs) were identified by the limma R package. Generally Applicable Gene-set Enrichment (GAGE), CIBERSORT algorithm, and Gene set variation analysis (GSVA) was utilized to access the functional, immune infiltration, and T helper 1/2/17 Chemokine signature changes in diseases with or without hair loss. qRT-PCR, immunofluorescence, and immunohistochemical staining were used to detect gene expression alteration among diseases from patients and mouse models. Results We identified shared gene expression changes associated with T cell chemotaxis and interferon-β response in scalp autoimmune diseases. In addition to the expected reduction in intermediate and keratin filaments, four functional changes associated with alopecia were found, including intestinal immune network for IgA, cell adhesion molecules, natural killer cell-mediated cytotoxicity, and complement and coagulation cascades. Immune infiltration analysis revealed increased infiltration of CD8 + T cells, NK cells, and mast cells in AA and CLE, while CD4 + cells were the predominant infiltrating immune cells in scalp psoriasis. Furthermore, scalp psoriasis exhibited a distinct Th17/Th1 profile, elevated CCL4 levels, and more CCR5 + Foxp3 + cells infiltration around the hair follicle. Conclusion Our study identified shared pathways and immune cells involved in hair loss and revealed a prominent perifollicular infiltration model of CD4 + T cells and an increased CCL4-CCR5 axis in scalp psoriasis, which may contribute to hair preservation in psoriasis patients. These findings provided valuable insights for developing therapeutic strategies for inflammatory alopecia.