Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, Palermo, Italy.
Department of Biopathology and Medical Biotechnologies (DIBIMED), University of Palermo, Palermo, Italy.
J Crohns Colitis. 2019 Jul 25;13(7):873-883. doi: 10.1093/ecco-jcc/jjz015.
Inflammatory bowel disease [IBD] is a complex chronic inflammatory disease of the human gut with no clear aetiology. Traditionally, dysregulated adaptive immune responses play an important role even though accumulating evidence suggests a role also for innate immunity. Because of the well-known plasticity of γδ T cells, we investigated their percentage occurrence, phenotypic features and effector functions in the intestinal mucosa of early-onset and long-standing IBD patients, as compared to healthy subjects.
Fresh biopsies from 30 Crohn's disease and ulcerative colitis patients were obtained and digested, and cells were analysed by flow cytometry.
We found a reduced frequency of Vδ1 T cells in tissue from early and late IBD patients (2.24% and 1.95%, respectively, vs 5.44% in healthy tissue) but an increased frequency of Vδ2 T cells in the gut of late IBD patients (3.19% in late patients vs 1.5% in early patients and 1.65% in healthy tissue). The infiltrating Vδ2 T cells had predominant effector memory and terminally differentiated phenotypes and produced elevated levels of tumour necrosis factor-α [TNF-α] and interleukin-17 [IL-17]. The frequency of tissue Vδ2 T cells correlated with the extent of the inflammatory response and the severity of IBD.
Our study shows that tissue Vδ1 T cells are decreased in IBD patients while Vδ2 T cells are increased in the gut of IBD patients and contribute to TNF-α production. Moreover, we identify an as yet unappreciated role of Vδ2 T cells in IL-17 production in the gut of long-standing IBD patients, suggesting that they also participate in the chronic inflammatory process.
炎症性肠病(IBD)是一种复杂的慢性人类肠道炎症性疾病,其病因尚不清楚。传统上,适应性免疫反应失调起着重要作用,尽管越来越多的证据表明固有免疫也起作用。由于 γδ T 细胞的众所周知的可塑性,我们研究了它们在早发型和长程 IBD 患者的肠道黏膜中的百分比发生、表型特征和效应功能,与健康受试者进行比较。
从 30 例克罗恩病和溃疡性结肠炎患者中获取新鲜活检并进行消化,通过流式细胞术分析细胞。
我们发现早期和晚期 IBD 患者组织中 Vδ1 T 细胞的频率降低(分别为 2.24%和 1.95%,而健康组织中为 5.44%),但晚期 IBD 患者肠道中 Vδ2 T 细胞的频率增加(晚期患者中为 3.19%,早期患者中为 1.5%,健康组织中为 1.65%)。浸润的 Vδ2 T 细胞具有主要的效应记忆和终末分化表型,并产生高水平的肿瘤坏死因子-α[TNF-α]和白细胞介素-17[IL-17]。组织 Vδ2 T 细胞的频率与炎症反应的程度和 IBD 的严重程度相关。
我们的研究表明,IBD 患者的组织 Vδ1 T 细胞减少,而 Vδ2 T 细胞在 IBD 患者的肠道中增加,并有助于 TNF-α的产生。此外,我们发现 Vδ2 T 细胞在长程 IBD 患者肠道中产生 IL-17 的作用尚未被认识,表明它们也参与慢性炎症过程。