Abbasova Vusala, Gül Ahmet, Saruhan-Direskeneli Güher
Department of Physiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Division of Rheumatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Immunol Lett. 2022 Feb;242:37-45. doi: 10.1016/j.imlet.2021.11.004. Epub 2021 Nov 24.
Involvement of γδ T cells is implicated in the pathogenesis of Behçet's disease (BD) as a bridge between innate and adaptive responses. IL-17 and IL-22 have also been shown to participate in the BD pathogenesis in addition to IFN-γ. Mainly CD4 T cells are investigated previously for the production of these inflammatory cytokines. In this study, the role of γδ T cells in cytokine-related mechanisms was evaluated in BD in comparison to CD4 T cells. Surface expression of markers for functional states of both CD4 and γδ T cells were compared in ex vivo samples collected from patients with BD and healthy controls (HC). Sixteen active BD (a-BD), 9 inactive BD (i-BD) patients and 25 HC were investigated. The expression of CD161, CCR6 as markers for IL-17 producing cells were analyzed on γδ and CD4 T cells. IFN-γ, IL-17A, IL-22, as well as CD107a (LAMP1) and CD16 (FcγRIII) were evaluated in both cell subtypes after in vitro stimulation. Only IFN-γ production was increased in γδ T cells of a-BD patients. There was no difference in increase of CD107a or decrease of CD16 surface expression on γδ T cells upon stimulation between the groups. Ex vivo IL-17A and both IL-17A/IFN-γ production and expression of CD161, CCR6 by CD4 T cells were increased in a-BD. Along with CD4 T cells, γδ T cells have complementary roles in cytokine production in BD. Higher IFN-γ production of γδ T cells suggests the role of an environmental triggers in BD pathogenesis, whereas IL-17 related activity is mainly provided by CD4 T cells.
γδ T细胞的参与作为先天性和适应性反应之间的桥梁，与白塞病（BD）的发病机制有关。除了IFN-γ外，IL-17和IL-22也已被证明参与BD的发病机制。以前主要研究CD4 T细胞产生这些炎性细胞因子的情况。在本研究中，与CD4 T细胞相比，评估了γδ T细胞在BD细胞因子相关机制中的作用。在从BD患者和健康对照（HC）收集的体外样本中比较了CD4和γδ T细胞功能状态标志物的表面表达。研究了16例活动期BD（a-BD）患者、9例非活动期BD（i-BD）患者和25例HC。分析了γδ和CD4 T细胞上作为产生IL-17细胞标志物的CD161、CCR6的表达。在体外刺激后，评估了两种细胞亚型中的IFN-γ、IL-17A、IL-22以及CD107a（LAMP1）和CD16（FcγRIII）。仅a-BD患者的γδ T细胞中IFN-γ产生增加。各组间刺激后γδ T细胞上CD107a增加或CD16表面表达降低没有差异。a-BD中，体外CD4 T细胞的IL-17A以及IL-17A/IFN-γ产生和CD161、CCR6表达增加。与CD4 T细胞一起，γδ T细胞在BD的细胞因子产生中具有互补作用。γδ T细胞较高的IFN-γ产生表明环境触发因素在BD发病机制中的作用，而IL-17相关活性主要由CD4 T细胞提供。
