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在麻风病中同时分析多个 T 辅助细胞亚群,揭示了在临床形式和反应性事件中 Th1、Th2、Th17 和 Tregs 标志物表达的不同模式。

Simultaneous analysis of multiple T helper subsets in leprosy reveals distinct patterns of Th1, Th2, Th17 and Tregs markers expression in clinical forms and reactional events.

机构信息

Instituto Lauro de Souza Lima, Rodovia Comandante João Ribeiro de Barros, Km 225/226, Bauru, São Paulo, 17034-971, Brazil.

Centro de Ciências da Saúde, Universidade do Sagrado Coração, Rua Irmã Arminda, 10-50, Jardim Brasil, Bauru, São Paulo, 17.011-160, Brazil.

出版信息

Med Microbiol Immunol. 2017 Dec;206(6):429-439. doi: 10.1007/s00430-017-0519-9. Epub 2017 Sep 5.

Abstract

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Previous studies have demonstrated that the difference among clinical forms of leprosy can be associated with the immune response of patients, mainly by T helper (Th) and regulatory T cells (Tregs). Then, aiming at clarifying the immune response, the expression of cytokines related to Th1, Th2, Th17 and Tregs profiles were evaluated by qPCR in 87 skin biopsies from leprosy patients. Additionally, cytokines and anti-PGL-1 antibodies were determined in serum by ELISA. The results showed that the expression of various targets (mRNA) related to Th1, Th2, Th17 and Tregs were significantly modulated in leprosy when compared with healthy individuals, suggesting the presence of a mixed profile. In addition, the targets related to Th1 predominated in the tuberculoid pole and side and Th2 and Tregs predominated in the lepromatous pole and side; however, Th17 targets showed a mixed profile. Concerning reactional events, Tregs markers were decreased and IL-15 was increased in reversal reaction and IL-17F, CCL20 and IL-8 in erythema nodosum leprosum, when compared with the respective non-reactional leprosy patients. Additionally, ELISA analysis demonstrated that IL-22, IL-6, IL-10 and anti-PGL-1 antibody levels were significantly higher in the serum of patients when compared with healthy individuals, and IL-10 and anti-PGL-1 antibodies were also increased in the lepromatous pole and side. Together, these results indicate that Th1, Th2 and Th17 are involved in the determination of clinical forms of leprosy and suggest that decreased Tregs activity may be involved in the pathogenesis of reactional events.

摘要

麻风病是由麻风分枝杆菌引起的慢性传染病。先前的研究表明,麻风病的临床形式差异可能与患者的免疫反应有关,主要是通过辅助性 T 细胞(Th)和调节性 T 细胞(Treg)。然后,为了阐明免疫反应,通过 qPCR 评估了 87 例麻风病患者皮肤活检中与 Th1、Th2、Th17 和 Treg 谱相关的细胞因子的表达。此外,通过 ELISA 测定血清中的细胞因子和抗 PGL-1 抗体。结果表明,与健康个体相比,麻风病患者的各种与 Th1、Th2、Th17 和 Treg 相关的靶标(mRNA)表达均显著调节,表明存在混合谱。此外,Th1 相关靶标在结核样型和侧位占优势,Th2 和 Treg 相关靶标在瘤型和侧位占优势;然而,Th17 相关靶标表现出混合谱。关于反应性事件,与相应的非反应性麻风病患者相比,逆转反应中 Treg 标志物减少,IL-15 增加,结节性红斑中 IL-17F、CCL20 和 IL-8 增加。此外,ELISA 分析表明,与健康个体相比,患者血清中的 IL-22、IL-6、IL-10 和抗 PGL-1 抗体水平显著升高,瘤型和侧位的 IL-10 和抗 PGL-1 抗体也升高。综上所述,这些结果表明 Th1、Th2 和 Th17 参与了麻风病临床形式的决定,并表明 Treg 活性降低可能与反应性事件的发病机制有关。

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