Ráki M, Schjetne K W, Stamnaes J, Molberg Ø, Jahnsen F L, Issekutz T B, Bogen B, Sollid L M
Institute of Immunology, The Pathology Clinic, Rikshospitalet-Radiumhospitalet Medical Center, University of Oslo, Oslo, Norway.
Scand J Immunol. 2007 Mar;65(3):213-20. doi: 10.1111/j.1365-3083.2006.01881.x.
Celiac disease is a chronic small intestinal inflammation driven by gluten-reactive T cells of the intestinal mucosa. These T cells are HLA-DQ2 or -DQ8 restricted, and predominantly recognize gluten peptides that are deamidated by the enzyme transglutaminase 2 (TG2). Our recent results strongly suggest that duodenal CD11c(+) dendritic cells (DC) are directly involved in T cell activation in the celiac lesion. The aim of this study was to investigate whether surface-associated TG2 could be involved in receptor-mediated endocytosis of gluten peptides, a process that may contribute to the preferential recognition of deamidated peptides. We found that both monocyte-derived DC and local CD11c(+) DC in the duodenal mucosa expressed cell surface-associated TG2. As phenotypic characterization of CD11c(+) DC in the celiac lesion suggests that these cells may be derived from circulating monocytes, we used monocyte-derived DC in functional in vitro studies. Using a functional T cell assay, we obtained evidence that cell surface-associated TG2 is endocytosed by monocyte-derived DC. However, we were unable to obtain evidence for a role of surface TG2 in the loading and subsequent generation of deamidated gluten peptides in these cells.
乳糜泻是一种由肠道黏膜中对麸质产生反应的T细胞驱动的慢性小肠炎症。这些T细胞受HLA-DQ2或-DQ8限制，主要识别被转谷氨酰胺酶2（TG2）脱酰胺的麸质肽。我们最近的研究结果强烈表明，十二指肠CD11c(+)树突状细胞（DC）直接参与乳糜泻病变中的T细胞活化。本研究的目的是调查表面相关的TG2是否参与麸质肽的受体介导的内吞作用，这一过程可能有助于优先识别脱酰胺肽。我们发现，单核细胞衍生的DC和十二指肠黏膜中的局部CD11c(+) DC均表达细胞表面相关的TG2。由于乳糜泻病变中CD11c(+) DC的表型特征表明这些细胞可能来源于循环单核细胞，因此我们在体外功能研究中使用了单核细胞衍生的DC。通过功能性T细胞检测，我们获得证据表明细胞表面相关的TG2被单核细胞衍生的DC内吞。然而，我们无法获得证据证明表面TG2在这些细胞中对脱酰胺麸质肽的负载及随后生成过程中所起的作用。
