背景:自身免疫性皮肤病如天疱疮[PF]中的T辅助因子相互作用和细胞因子监测可能在预测病理的临床分层中起重要作用。
目的:为了评估CD4+T细胞失衡,[i]本研究旨在评估相关的免疫细胞[Th1,Th2,Th17和Treg细胞]以及相关的细胞因子[IL-1β,IFNγ,IL-2、IL-4、IL-5、IL-6、IL-8、IL-10、IL-12p70、IL-17A、IL-17F,IL-22,TNF-β,和外周血中的TNFα,和[ii]在临床过程中,它们在PF地方性患者的病变皮肤中各自的转录因子。
方法:采用流式细胞术对22例PF患者的外周血进行分析,通过14种细胞因子的多重珠分析,评估Th细胞亚群及其特征性细胞因子的功能关联。使用TaqMan检测系统分析其相关转录因子的皮肤mRNA表达。
结果:我们的发现表明,与健康对照[HC]相比,PF患者中的CD4T细胞亚型的特征在于[i]相似的Th1/Th2比率和增加的Th17/Treg比率和[ii]Th-17特异性细胞因子的血浆水平显着升高;IL-6,IL-8,IL-17A。Th17和Treg亚型的百分比较高,血浆IL-17F水平的显着增加在复发性PF患者中维持,争论Th17细胞在PF发病机制中的关键作用。此外,我们的研究结果指出了促炎细胞因子IL-6的主要贡献.的确,除了参与疾病发展的初始阶段,IL-6似乎也参与病理生理过程的维持,可能是通过其对Th17分化的影响。复发性PF患者的FOXP3和TBET的皮肤相关mRNA表达水平明显高于新生PF患者。
结论:我们的结果强调了Th17淋巴细胞及其相关的促炎细胞因子在疾病的临床过程中发挥的核心作用,扭转PF中的Th1/Th2二分法。
BACKGROUND: T helper interplay and cytokines monitoring in auto-immune skin disorders such as
Pemphigus Foliaceus [PF] may play a central role in predicting the clinical stratification of the pathology.
OBJECTIVE: In order to assess the CD4+ T cell imbalance, [i] this study aims to assess the related immune cells [Th1, Th2, Th17, and Treg cells] as well as the related cytokines [IL-1β, IFNγ, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-17F, IL- 22, TNF-β, and TNFα] in peripheral blood, and [ii] their respective transcription factors in the lesioned skin of PF endemic patients during the clinical course.
METHODS: Peripheral blood of 22 PF patients was analyzed by flow cytometry to assess the functional associations of Th cell subpopulations and their characteristic cytokines by multiplex bead assay of 14-plex cytokines. Skin mRNA expression of their associated transcription factors was analyzed using the TaqMan detection system.
RESULTS: Our findings revealed that the CD4+ T cell subtypes in PF patients compared to Healthy Controls [HC] were characterized by [i] a similar Th1/Th2 ratio and increased Th17/Treg ratio and [ii] significantly higher plasma levels of Th-17 specific cytokines; IL- 6, IL-8, IL-17A. Higher percentages in Th17 and Treg subtypes and a significant increase in plasma IL-17F levels were maintained in relapsing PF patients, arguing the pivotal role of Th17 cells in PF pathogenesis. Furthermore, our findings pointed out the major contribution of the pro-inflammatory cytokine IL-6. Indeed, in addition to being involved in the initial stages of disease development, IL-6 seems to also be involved in the maintenance of the pathophysiological process, probably through its effect on Th17 differentiation. The skin-relative mRNA expression levels of FOXP3 and TBET were significantly higher in relapsing PF patients compared to de novo PF patients.
CONCLUSIONS: Our results highlight the central role played by Th17 lymphocytes and their related pro-inflammatory cytokines during the clinical course of the disease, reversing the Th1/Th2 dichotomy in PF.