皮肤固有记忆性 CD8+T 细胞可区分银屑病关节炎与银屑病。

OBJECTIVE: To compare immune cell phenotype and function in psoriatic arthritis (PsA) versus psoriasis in order to better understand the pathogenesis of PsA. METHODS: In-depth immunophenotyping of different T cell and dendritic cell subsets was performed in patients with PsA, psoriasis, or axial spondyloarthritis and healthy controls. Subsequently, we analyzed cells from peripheral blood, synovial fluid (SF), and skin biopsy specimens using flow cytometry, along with high-throughput transcriptome analyses and functional assays on the specific cell populations that appeared to differentiate PsA from psoriasis. RESULTS: Compared to healthy controls, the peripheral blood of patients with PsA was characterized by an increase in regulatory CD4+ T cells and interleukin-17A (IL-17A) and IL-22 coproducing CD8+ T cells. One population specifically differentiated PsA from psoriasis: i.e., CD8+CCR10+ T cells were enriched in PsA. CD8+CCR10+ T cells expressed high levels of DNAX accessory molecule 1 and were effector memory cells that coexpressed skin-homing receptors CCR4 and cutaneous lymphocyte antigen. CD8+CCR10+ T cells were detected under inflammatory and homeostatic conditions in skin, but were not enriched in SF. Gene profiling further revealed that CD8+CCR10+ T cells expressed GATA3, FOXP3, and core transcriptional signature of tissue-resident memory T cells, including CD103. Specific genes, including RORC, IFNAR1, and ERAP1, were up-regulated in PsA compared to psoriasis. CD8+CCR10+ T cells were endowed with a Tc2/22-like cytokine profile, lacked cytotoxic potential, and displayed overall regulatory function. CONCLUSION: Tissue-resident memory CD8+ T cells derived from the skin are enhanced in the circulation of patients with PsA compared to patients with psoriasis alone. This may indicate that aberrances in cutaneous tissue homeostasis contribute to arthritis development.

目的：比较银屑病关节炎（PsA）与银屑病患者的免疫细胞表型和功能，以更好地了解 PsA 的发病机制。

方法：对 PsA、银屑病或中轴型脊柱关节炎患者及健康对照者进行不同 T 细胞和树突状细胞亚群的深入免疫表型分析。随后，我们使用流式细胞术分析外周血、滑液（SF）和皮肤活检标本中的细胞，并对似乎将 PsA 与银屑病区分开的特定细胞群进行高通量转录组分析和功能检测。

结果：与健康对照者相比，PsA 患者的外周血以调节性 CD4+T 细胞和白细胞介素-17A（IL-17A）和 IL-22 共产生 CD8+T 细胞增加为特征。一个特定的群体将 PsA 与银屑病区分开来：即，CD8+CCR10+T 细胞在 PsA 中富集。CD8+CCR10+T 细胞表达高水平的 DNAX 辅助分子 1，并且是共表达皮肤归巢受体 CCR4 和皮肤淋巴细胞抗原的效应记忆细胞。CD8+CCR10+T 细胞在皮肤的炎症和稳态条件下被检测到，但在 SF 中没有富集。基因谱进一步显示，CD8+CCR10+T 细胞表达 GATA3、FOXP3 和组织驻留记忆 T 细胞的核心转录特征，包括 CD103。与银屑病相比，PsA 中特定基因，包括 RORC、IFNAR1 和 ERAP1，上调。CD8+CCR10+T 细胞具有 Tc2/22 样细胞因子谱，缺乏细胞毒性潜力，并表现出整体调节功能。

结论：与单独患有银屑病的患者相比，PsA 患者的循环中存在来自皮肤的组织驻留记忆 CD8+T 细胞增强。这可能表明皮肤组织稳态异常导致关节炎的发展。