Inés Moret-Tatay, Pilar Nos, Marisa Iborra, Francisco Rausell, Belén Beltrán
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引用次数: 0
摘要
克罗恩病(Crohn's disease,CD)是一种慢性复发性炎症性疾病,据推测,粘膜 T 细胞凋亡缺陷会产生持续的炎症和活性氧积累。CD的T细胞是否对凋亡具有内在抵抗力,或者这种抵抗力是否是在肠道部位获得的,这些都需要加以澄清,因为细胞机制会调节这些细胞凋亡受损的情况。在这里,我们分析了发病时未接受特定 CD 治疗的患者和健康对照组的外周血 T 细胞。我们培养了未活化的新鲜纯化淋巴细胞,并对其进行了体外活化(CD3/CD28 抗体)和凋亡(Fas 抗体)检测。细胞通过流式细胞术进行分析。对 Caspases(3、8 和 9)和过氧化氢酶活性进行了测定;通过 Western 印迹法检测了 bax、Bcl-2 和 NF-kB 的蛋白水平;通过基于 Luminex 的检测法检测了细胞因子。结果显示,CD患者的CD4 T细胞在迁移到肠道粘膜之前不易发生凋亡。结果显示,CD患者的Caspase-9、FasR、sIL-2Rα、IL-17A、IFNγ、IL-6、TNF-α和IL-10有显著差异,而其他被分析的生物因子则无显著差异。CD T细胞的过氧化氢酶活性明显降低,这一点在体外实验中得到了证实,在健康对照组的T细胞中抑制过氧化氢酶会以剂量依赖的方式引发细胞凋亡抑制。总之,CD T 细胞的凋亡抑制是这些细胞迁移到肠道粘膜之前的一个特征。值得注意的是,过氧化氢酶抑制剂可直接影响 T 细胞的凋亡。
Catalase inhibition can modulate the ability of peripheral blood T cells to undergo apoptosis in Crohn's disease.
Crohn's disease (CD) is a chronic relapsing inflammatory disorder in which defective apoptosis of mucosal T cells is postulated to produce sustained inflammation and reactive oxygen species accumulation. Whether CD T cells are intrinsically resistant to apoptosis or whether this resistance is acquired at the intestinal site needs to be clarified, as the cellular mechanisms modulate the impaired apoptosis in these cells. Here, we analysed peripheral blood T cells from patients naïve to specific CD treatment at the onset and from healthy controls. Non-activated freshly purified lymphocytes were cultured and submitted to in vitro protocols for activation (CD3/CD28 antibodies) and apoptosis (Fas antibody). Cells were analysed by flow cytometry. Caspases (3, 8, and 9) and catalase activity were measured; protein levels of bax, Bcl-2, and NF-kB were detected by western blotting, and cytokines by Luminex-based assays. The results showed that CD4 T cells from CD patients are less prone to apoptosis before they can migrate to the intestinal mucosa. Caspase-9, FasR, sIL-2Rα, IL-17A, IFNγ, IL-6, TNF-α, and IL-10 were shown to be significantly different in CD but not for the rest of the analysed biological elements. Catalase activity was significantly reduced in CD T cells, which was confirmed in ex vivo experiments in which catalase inhibition in T cells from healthy controls triggered apoptosis inhibition in a dose-dependent manner. In conclusion, apoptosis inhibition of CD T cells is a feature of these cells before they can migrate to the intestinal mucosa. Noteworthy, the impaired apoptosis of T cells can be directly influenced by catalase inhibition.
期刊介绍:
Clinical & Experimental Immunology (established in 1966) is an authoritative international journal publishing high-quality research studies in translational and clinical immunology that have the potential to transform our understanding of the immunopathology of human disease and/or change clinical practice.
The journal is focused on translational and clinical immunology and is among the foremost journals in this field, attracting high-quality papers from across the world. Translation is viewed as a process of applying ideas, insights and discoveries generated through scientific studies to the treatment, prevention or diagnosis of human disease. Clinical immunology has evolved as a field to encompass the application of state-of-the-art technologies such as next-generation sequencing, metagenomics and high-dimensional phenotyping to understand mechanisms that govern the outcomes of clinical trials.