Format

Send to

Choose Destination
Diabetes. 2010 Sep;59(9):2237-46. doi: 10.2337/db10-0147. Epub 2010 Jun 14.

Inflammatory tendencies and overproduction of IL-17 in the colon of young NOD mice are counteracted with diet change.

Author information

1
Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.

Abstract

OBJECTIVE:

Dietary factors influence diabetes development in the NOD mouse. Diet affects the composition of microbiota in the distal intestine, which may subsequently influence intestinal immune homeostasis. However, the specific effects of antidiabetogenic diets on gut immunity and the explicit associations between intestinal immune disruption and type 1 diabetes onset remain unclear.

RESEARCH DESIGN AND METHODS:

Gut microbiota of NOD mice fed a conventional diet or ProSobee formula were compared using gas chromatography. Colonic lamina propria immune cells were characterized in terms of activation markers, cytokine mRNA and Th17 and Foxp3(+) T-cell numbers, using real-time PCR and flow cytometry. Activation of diabetogenic CD4 T-cells by purified B-cells was assessed in both groups. Immune tolerance to autologous commensal bacteria was evaluated in vitro using thymidine-incorporation tests.

RESULTS:

Young NOD mice showed a disturbed tolerance to autologous commensal bacteria. Increased numbers of activated CD4 T-cells and (CD11b(+)CD11c(+)) dendritic cells and elevated levels of Th17 cells and IL23 mRNA were moreover observed in colon lamina propria. These phenomena were abolished when mice were fed an antidiabetogenic diet. The antidiabetogenic diet also altered the expression levels of costimulatory molecules and the capacity of peritoneal B-cells to induce insulin-specific CD4 T-cell proliferation.

CONCLUSIONS:

Young NOD mice show signs of subclinical colitis, but the symptoms are alleviated by a diet change to an antidiabetogenic diet. Disrupted immune tolerance in the distal intestine may influence peritoneal cell pools and B-cell-mediated activation of diabetogenic T-cells.

PMID:
20547977
PMCID:
PMC2927946
DOI:
10.2337/db10-0147
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center