Gianfrani Carmen, Auricchio Salvatore, Troncone Riccardo
Institute of Food Science and Technology, CNR, Avellino, Italy.
Immunol Lett. 2005 Jul 15;99(2):141-5. doi: 10.1016/j.imlet.2005.02.017. Epub 2005 Apr 7.
Celiac disease (CD) is a complex small intestinal disorder due to a dysregulated immune response to wheat gliadin and related proteins which leads to a small intestinal enteropathy. It is generally accepted that CD is a T-cell mediated disease, in which, gliadin derived peptides, either in native form or deamidated by tissue transglutaminase, activate lamina propria infiltrating T lymphocytes which release proinflammatory cytokines. Recent studies indicate that gliadin contains also peptides able to activate an innate immune response. In particular, they induce a selective expansion of IEL, particularly TCRgamma/delta+ and CD8+TCR alpha/beta+ lymphocytes bearing the CD94 NK receptor, as well as a strong epithelial expression of MICA molecules which interact with NKG2D receptor expressed on TCRgamma/delta+ and NK cells. Most of the events of innate immune activation events are inhibited by antibodies neutralizing IL-15, thus confirming the key role of this cytokine as a mediator of intestinal mucosa damage induced by ingestion of gliadin. It remains to be established to what extent the ability of gliadin peptides to activate innate immunity relates to other biological properties exerted not only on celiac cells and tissues; the specificity of celiac patients is probably related to their genetic make up.
乳糜泻（CD）是一种复杂的小肠疾病，由对小麦醇溶蛋白及相关蛋白的免疫反应失调所致，会引发小肠肠病。普遍认为CD是一种T细胞介导的疾病，其中，醇溶蛋白衍生肽，无论是天然形式还是经组织转谷氨酰胺酶脱酰胺的形式，都会激活固有层浸润性T淋巴细胞，这些细胞会释放促炎细胞因子。最近的研究表明，醇溶蛋白还含有能够激活固有免疫反应的肽。具体而言，它们会诱导肠上皮内淋巴细胞（IEL）选择性扩增，尤其是携带CD94 NK受体的TCRγ/δ+和CD8+TCRα/β+淋巴细胞，以及与TCRγ/δ+和NK细胞上表达的NKG2D受体相互作用的MICA分子在上皮细胞中的强烈表达。大多数固有免疫激活事件会被中和IL-15的抗体抑制，从而证实了这种细胞因子作为摄入醇溶蛋白诱导的肠黏膜损伤介质的关键作用。醇溶蛋白肽激活固有免疫的能力在多大程度上与不仅对乳糜泻细胞和组织发挥的其他生物学特性相关，仍有待确定；乳糜泻患者的特异性可能与其基因构成有关。
