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Summary  The interplay between diet and immune parameters which could affect type 1 diabetes ( T 1 D ) pathogenesis is not sufficiently clarified. Intestinal up‐regulation of the activating receptor natural killer group 2D ( NKG 2 D)  ( CD 314) and its ligands is a hallmark of coeliac disease. However, the direct effect of gluten on  NKG 2 D  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  NKG 2 D  expression on DX5 + (CD49b) natural killer ( NK)  cells,  CD 8 +   T  cells and in intestinal and islet levels of  NKG 2 D  and ligands in  BALB /c and non‐obese diabetic ( NOD)  mice. Gluten‐free  NOD  mice had lower insulitis ( P  &lt; 0·0001); reduced expression of  NKG 2 D  on  DX 5 +   NK cell s in spleen and auricular lymph nodes ( P  &lt; 0·05); and on  CD 8 +   T  cells in pancreas‐associated lymph nodes ( P  = 0·04). Moreover, the level of  CD 71 on  DX 5 +   NK  cells and  CD 8 +   T  cells ( P  &lt; 0·005) was markedly reduced.  GF  and  SGF  mice had reduced expression of  NKG 2 D  and  DX 5 m RNA  in intestine ( P  &lt; 0·05). Differences in intestinal m RNA  expression were found in mice at 8, 13 and 20 weeks. Intestinal expression of  NKG 2 D  ligands was reduced in  SGF  mice with lower expression of all ligands. In isolated islets, a  SGF  diet induced a higher expression of specific  NKG 2 D  ligands. Our data show that a gluten‐free diet reduces the level of  NKG 2 D  and the expression of  NKG 2 D  ligands. These immunological changes may contribute to the lower  T 1 D  incidence associated with a gluten‐free diet.

A gluten‐free diet lowers NKG2D and ligand expression in BALB /c and non‐obese diabetic (NOD) mice