J Biol Regul Homeost Agents. 2012 Apr-Jun;26(2):171-9.
Despite intense investigation, the pathogenetic mechanisms leading to villous atrophy in Celiac disease (CD) remain not completely understood. The traditional interpretation is that CD4 cells recognize gliadin and develop an inflammatory reaction by production of Th1 cytokines at the mucosa level inducing CD8 cells to kill mucosal cells by a direct cytotoxic mechanism or by Fas-mediated apoptosis. Recent data, however, have shown that novel CD4 T-cells subpopulations, CD4+ CD25+ Regulatory T cells (Tregs) and Th17 cells also play a role in the ongoing inflammatory process. Both Tregs and Th17 cells are increased in active CD. However, because Tregs have a suppressive activity on inflammation, their role is controversial. In this editorial we discuss these recent findings and the hypothesis formulated to explain the increase of Tregs. To understand the pathogenesis of tissue damage of CD, we have focused on the duodenal micro-environment, introducing the new concept of immunological niche that in CD summarizes cellular and cytokine interactions in duodenal mucosa, where a high plasticity of T-cell subsets is present. CD is often complicated by T-cell lymphomas, especially in cases of refractory CD.
尽管进行了深入的研究，但导致乳糜泻（CD）绒毛萎缩的发病机制仍不完全清楚。传统的解释是，CD4 细胞识别麦胶蛋白，并通过在黏膜水平产生 Th1 细胞因子来引发炎症反应，从而诱导 CD8 细胞通过直接细胞毒性机制或 Fas 介导的细胞凋亡杀死黏膜细胞。然而，最近的数据表明，新型 CD4 T 细胞亚群，即 CD4+CD25+调节性 T 细胞（Tregs）和 Th17 细胞，也在持续的炎症过程中发挥作用。Tregs 和 Th17 细胞在活动性 CD 中均增加。然而，由于 Tregs 对炎症具有抑制作用，因此其作用存在争议。在这篇社论中，我们讨论了这些最新发现以及为解释 Tregs 增加而提出的假设。为了了解 CD 组织损伤的发病机制，我们专注于十二指肠微环境，引入了免疫生态位的新概念，该概念概括了十二指肠黏膜中的细胞和细胞因子相互作用，其中 T 细胞亚群具有很高的可塑性。CD 常伴有 T 细胞淋巴瘤，尤其是在难治性 CD 病例中。
