Abstract
The innate immune system is known to play an important role in oral tolerance to dietary antigens. 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 particularly 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 reverse transcription-quantitative polymerase chain reaction (qRT-PCR), if dietary gluten induces changes in the activation of DCs and distribution of selected innate cells in lymphoid, pancreatic and intestinal tissues in BALB/c and NOD mice. We found that a GF diet increased 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 NOD mice and increases expression of DC activation markers in NOD mice. These results contribute to the explanation of the low diabetes incidence in GF NOD mice. This mechanism may be important in development of type 1 diabetes, celiac disease and non-celiac gluten sensitivity.
Highlights
Oral tolerance to dietary antigens is important in healthy individuals and relies on the innate immune system and presentation by dendritic cells (DCs) [1]
We examined the composition of different innate populations in spleen from 13-week-old BALB/c and NOD mice receiving STD gluten-containing diet and GF diet from the age of 4 weeks
In NOD mice we found a 13.5% increase in CD11c+ cells, a marker for DCs, in animals receiving the GF diet compared to animals on a STD diet (p = 0.035, Fig. 1A)
Summary
Oral tolerance to dietary antigens is important in healthy individuals and relies on the innate immune system and presentation by dendritic cells (DCs) [1]. In celiac disease (CD), intolerance to indigestible wheat gluten proteins results in chronic intestinal inflammation [2]. Gluten and Innate Cells in BALB/c and NOD Mice (GF) diet has been shown to prevent diabetes in NOD mice [5] and Biobreeding (BB) rats [6]. T1D patients without CD have an abnormal gluten response [7,8], and a gluten-free diet is reported to halt disease progression in a case study [9]. Both T1D and CD share high susceptibility associated with the HLA-DQ2 and HLA-DQ8 haplotypes [10,11]
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