Single-cell RNA sequencing reveals the interaction of TREM2+ macrophages and Tc17 lymphocytes in scalp psoriasis.

Scalp psoriasis exhibits unique clinical features and relative resistance to conventional therapies compared with lesions on other body sites. However, the immune landscape underlying these characteristics preferentially observed in scalp lesions remains poorly understood. To characterize immune-cell heterogeneity and site-associated intercellular interactions in scalp psoriasis, with a focus on inflammatory T-cell and myeloid-cell programs that may contribute to persistent local inflammation. We performed single-cell RNA sequencing on CD45⁺ immune cells isolated from scalp and body plaque lesions of patients with psoriasis, along with healthy controls. A total of 41,438 immune cells were subjected to downstream analyses including clustering, gene set enrichment, pseudotime trajectory inference, and CellChat-based intercellular interaction modeling. Spatial co-localization was validated using multiplex immunofluorescence. Scalp lesions showed a marked enrichment of IL-17⁺ CD8⁺ tissue-resident memory T (Tc17) cells, characterized by co-expression of IFNG and the lipid transporter FATP2 (SLC27A2). Pseudotime analysis revealed a transition from IL7R⁺ tissue-resident memory T cells to Tc17 cells, preferentially occurring in the scalp. TREM2⁺ macrophages in scalp lesions displayed elevated inflammatory and antigen-presentation signatures, including increased MHC-I expression. CellChat identified strengthened MHC-I-mediated interactions between TREM2⁺ macrophages and Tc17 cells in the scalp, which were corroborated by immunofluorescence demonstrating co-localization of FATP2⁺ Tc17 and TREM2⁺ macrophages around sebaceous units. This study identifies a scalp-enriched immune interaction involving TREM2⁺ macrophages and FATP2⁺ Tc17 cells, which may contribute to the persistence and localized nature of inflammation in scalp psoriasis.Trial registration: Not applicable.