Arvesen Amalie, Teunissen Marcel B M, Agerbæk Sofie, Kromann Bjørn, Bruun Pilgaard Møller Line, Gehad Ahmed, Clark Rachael A, Løvendorf Marianne Bengtson, Dyring-Andersen Beatrice
Department of Dermatology, Zealand University Hospital, 4600 Roskilde, Denmark.
Department of Dermatology, Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam University Medical Centers, Location AMC, 1105 AZ Amsterdam, The Netherlands.
Int J Mol Sci. 2025 Aug 18;26(16):7942. doi: 10.3390/ijms26167942.
T lymphocytes in human skin play essential roles in immune surveillance and tissue homeostasis, with distinct populations residing in the epidermal and dermal compartments. To characterize the molecular basis of their compartmentalized functional specialization, we performed proteomic analysis of total T cell populations isolated from healthy human skin, combining flow cytometry and liquid chromatography-tandem mass spectrometry. We quantified 5985 proteins across epidermal and dermal T cell populations, identifying 2177 significantly differentially expressed proteins (FDR < 0.05), including 1008 with >2-fold changes. Compared with dermal T cells, epidermal T cells showed elevated intensity of tissueresidency marker CD69, co-stimulatory protein CD27, complement components (C3, C4a, and Factors B and D), and proteins involved in oxidative phosphorylation and cholesterol metabolism. Epidermal T cells also exhibited higher levels of antimicrobial S100 proteins, chemokine receptor CCR6, IL-18, and MHC class I molecules, while, in contrast, dermal T cells showed increased expression of CXCR4, IL-16, and MHC class II-related proteins. While these distinct proteomic signatures suggest compartment-specific adaptations in metabolism, immune surveillance, and antigen presentation, the results should be interpreted as exploratory, given methodological limitations. Nonetheless, this study provides a valuable molecular resource for understanding the specialization of T cells within different skin layers and offers a basis for future investigations into skin immune biology and its potential implications in disease.
人类皮肤中的T淋巴细胞在免疫监视和组织稳态中发挥着重要作用，不同的T细胞群体存在于表皮和真皮层。为了阐明其区域性功能特化的分子基础，我们结合流式细胞术和液相色谱-串联质谱技术，对从健康人皮肤中分离出的总T细胞群体进行了蛋白质组学分析。我们对表皮和真皮T细胞群体中的5985种蛋白质进行了定量分析，鉴定出2177种差异表达显著的蛋白质（FDR<0.05），其中1008种蛋白质的变化倍数大于2倍。与真皮T细胞相比，表皮T细胞的组织驻留标志物CD69、共刺激蛋白CD27、补体成分（C3、C4a以及B因子和D因子）以及参与氧化磷酸化和胆固醇代谢的蛋白质的表达强度更高。表皮T细胞还表现出较高水平的抗菌S100蛋白、趋化因子受体CCR6、IL-18和MHC I类分子，而真皮T细胞则相反，其CXCR4、IL-16和MHC II类相关蛋白的表达增加。尽管这些独特的蛋白质组学特征表明在代谢、免疫监视和抗原呈递方面存在区域特异性适应，但鉴于方法学的局限性，这些结果应被视为探索性的。尽管如此，本研究为理解不同皮肤层中T细胞的特化提供了宝贵的分子资源，并为未来研究皮肤免疫生物学及其在疾病中的潜在影响提供了基础。
