RESEARCH ARTICLE Effect of Dietary Gluten on Dendritic Cells and Innate Immune Subsets in BALB/c and

The innate immune system is known to play an important role in oral tolerance to dietary an-tigens. This is important in development of celiac disease (CD) but may also be important in type 1 diabetes (T1D), and could potentially explain the reduced incidence of T1D in mice receiving a gluten-free (GF) diet. The direct in vivo effect of gluten on innate cells, and partic-ularly dendritic cells (DC) is not sufficiently clarified. Therefore, we wished to investigate the innate cell populations of spontaneous diabetic NOD mice and healthy BALB/c mice kept on a GF or a standard (STD) gluten containing diet. We studied, by flow cytometry and re-verse transcription-quantitative polymerase chain reaction (qRT-PCR), if dietary gluten in-duces changes in the activation of DCs and distribution of selected innate cells in lymphoid, pancreatic and intestinal tissues in BALB/c and NODmice. We found that a GF diet in-creased the percentage of macrophages in BALB/c spleen and of CD11c+ DCs in BALB/c and NOD spleen. Strictly gluten-free (SGF) diet increased the percentage of CD103+ DCs in BALB/c mice and decreased percentages of CD11b+ DCs in mesenteric and pancreatic lymph nodes in BALB/c mice. SGF diet in BALB/c mice also decreased DC expression of CD40, CCR7 and MHC-II in pancreatic lymph nodes. In conclusion, GF diet changes the composition of the innate immune system in BALB/c and NODmice and increases expres-sion of DC activation markers in NOD mice. These results contribute to the explanation of the low diabetes incidence in GF NODmice. This mechanism may be important in develop-ment of type 1 diabetes, celiac disease and non-celiac gluten sensitivity