Diabetes and Celiac Disease Unit, Lund University, Malmö, Sweden.
Clin Exp Immunol. 2014 Aug;177(2):391-403. doi: 10.1111/cei.12340.
The interplay between diet and immune parameters which could affect type 1 diabetes (T1D) pathogenesis is not sufficiently clarified. Intestinal up-regulation of the activating receptor natural killer group 2D (NKG2D) (CD314) and its ligands is a hallmark of coeliac disease. However, the direct effect of gluten on NKG2D expression is not known. We studied, by fluorescence activated cell sorter (lymphoid tissues) and reverse transcription-quantitative polymerase chain reaction (intestine and pancreatic islets), if a gluten-free diet (GF diet) from 4 weeks of age or a gluten-free diet introduced in breeding pairs (SGF diet), induced changes in NKG2D expression on DX5(+) (CD49b) natural killer (NK) cells, CD8(+) T cells and in intestinal and islet levels of NKG2D and ligands in BALB/c and non-obese diabetic (NOD) mice. Gluten-free NOD mice had lower insulitis (P < 0·0001); reduced expression of NKG2D on DX5(+) NK cells in spleen and auricular lymph nodes (P < 0·05); and on CD8(+) T cells in pancreas-associated lymph nodes (P = 0·04). Moreover, the level of CD71 on DX5(+) NK cells and CD8(+) T cells (P < 0·005) was markedly reduced. GF and SGF mice had reduced expression of NKG2D and DX5 mRNA in intestine (P < 0·05). Differences in intestinal mRNA expression were found in mice at 8, 13 and 20 weeks. Intestinal expression of NKG2D ligands was reduced in SGF mice with lower expression of all ligands. In isolated islets, a SGF diet induced a higher expression of specific NKG2D ligands. Our data show that a gluten-free diet reduces the level of NKG2D and the expression of NKG2D ligands. These immunological changes may contribute to the lower T1D incidence associated with a gluten-free diet.
饮食与免疫参数之间的相互作用可能会影响 1 型糖尿病（T1D）的发病机制，但目前尚不清楚。肠道中激活受体自然杀伤组 2D（NKG2D）（CD314）及其配体的上调是乳糜泻的一个标志。然而，目前尚不清楚麸质对 NKG2D 表达的直接影响。我们通过荧光激活细胞分选（淋巴组织）和逆转录定量聚合酶链反应（肠道和胰岛）研究了从 4 周龄开始进行无麸质饮食（GF 饮食）或在繁殖对中引入无麸质饮食（SGF 饮食）是否会改变 BALB/c 和非肥胖型糖尿病（NOD）小鼠 DX5（+）（CD49b）自然杀伤（NK）细胞、CD8（+）T 细胞以及肠道和胰岛中 NKG2D 和配体的表达。无麸质 NOD 小鼠的胰岛炎程度较低（P<0.0001）；脾脏和耳下淋巴结中 DX5（+）NK 细胞上 NKG2D 的表达减少（P<0.05）；胰腺相关淋巴结中 CD8（+）T 细胞上 NKG2D 的表达减少（P=0.04）。此外，DX5（+）NK 细胞和 CD8（+）T 细胞上 CD71 的水平明显降低（P<0.005）。GF 和 SGF 小鼠的肠道 NKG2D 和 DX5 mRNA 表达减少（P<0.05）。在 8、13 和 20 周时，在不同的小鼠中发现了肠道 mRNA 表达的差异。SGF 小鼠的肠道 NKG2D 配体表达降低，所有配体的表达均降低。在分离的胰岛中，SGF 饮食诱导特定 NKG2D 配体的表达增加。我们的数据表明，无麸质饮食降低了 NKG2D 水平和 NKG2D 配体的表达。这些免疫变化可能有助于降低与无麸质饮食相关的 1 型糖尿病发病率。
