Institute of Food Sciences, CNR, 83100 Avellino, Italy.
Gastroenterology Department, San G. Moscati Hospital, 83100 Avellino, Italy.
Cytokine. 2019 May;117:23-29. doi: 10.1016/j.cyto.2019.02.004. Epub 2019 Feb 18.
Enzymatic transamidation of wheat gliadin by microbial transglutaminase inhibits IFN-γ secretion by intestinal T cell lines from celiac disease (CD) patients. Here, we analysed its effects on intestinal biopsies from CD patients and studied the underlying mechanisms in HLA-DQ8 transgenic (tg) mice, a model of T-cell mediated gluten sensitivity. In vitro challenge with a soluble form of transamidated gliadin (spf) upregulated IL-10 transcript levels in human biopsy samples. Furthermore, the ratio of IL-10/IFN-γ transcripts was significantly increased following treatment with spf. In DQ8 tg mice, recall responses in vitro in the presence of dendritic cells pulsed with transamidated gliadin showed that gliadin-specific CD4 T cells did not produce IFN-γ at any tested dose. On the contrary, spf-specific CD4 T cells still secreted IFN-γ, but they also produced significant levels of IL-10 with both native and transamidated gliadin. Interestingly, this anti-inflammatory activity was restricted to a specific reverse-phase high-pressure liquid chromatography (RP-HPLC) fraction encompassing α-gliadins. These findings suggested an ability of transamidated gliadin to revert, as well as to prevent, the inflammatory phenotype triggered by native gliadin. This property was intrinsically associated with specific components of the α-gliadin fraction.
通过微生物谷氨酰胺转氨酶对小麦醇溶蛋白进行酶转酰胺作用，可抑制乳糜泻患者肠 T 细胞系分泌 IFN-γ。在这里，我们分析了它对乳糜泻患者肠道活检样本的影响，并在 HLA-DQ8 转基因（tg）小鼠中研究了其潜在机制，后者是一种 T 细胞介导的麸质敏感性模型。在体外用可溶形式的转酰胺醇溶蛋白（spf）刺激后，人活检样本中 IL-10 转录本水平上调。此外，spf 处理后 IL-10/IFN-γ 转录本的比值显著增加。在 DQ8 tg 小鼠中，在树突状细胞脉冲处理转酰胺醇溶蛋白存在的情况下进行体外回忆反应表明，在任何测试剂量下，特异性针对醇溶蛋白的 CD4 T 细胞均不产生 IFN-γ。相反，spf 特异性 CD4 T 细胞仍分泌 IFN-γ，但它们也使用天然和转酰胺醇溶蛋白产生显著水平的 IL-10。有趣的是，这种抗炎活性仅限于特定的反相高效液相色谱（RP-HPLC）包含α-醇溶蛋白的馏分。这些发现表明转酰胺醇溶蛋白具有逆转以及预防天然醇溶蛋白触发的炎症表型的能力。这种特性与α-醇溶蛋白馏分的特定成分内在相关。
