This vaccine immunized into prediabetic NOD mice subcutaneously could induce IL-10 and TGF-β expressing pTregs and lead to suppressing autoreactive T cells responses, resulting in the prevention of T1D in these animals.
We studied these issues by expressing human AIRE (huAIRE) as a modifier of tolerance function in NOD mice wherein the defects of thymic and peripheral tolerance together cause type I diabetes (T1D).
Since NOD mice is a well-established mouse model of T1D, MAIT cells were studied in these mice to evaluate their potential involvement in disease development.
ORMDL3 levels in islets from NOD mice, a mouse model for T1D in humans, showed a mild increase before diabetes onset, but a gradual decrease subsequently.
Two children with rapid and three children with slow beta cell function loss (as assessed by C-peptide AUC change in the mixed-meal tolerance tests performed 1 and 12 months after type 1 diabetes onset), participating in an ongoing trial with gluten-free diet, donated faeces, which were transferred into germ-free NOD mice.
We further investigated the mechanisms leading to accumulation of β-catenin in NOD DC and its role in the inflammatory pathogenic responses associated with T1D.
The relative frequency of different LNSC subsets was altered in both donors with type 1 diabetes and NOD mice, and both MHC class II and programmed death-ligand 1 (PD-L1) expression were upregulated in human type 1 diabetes.
We observed that ASD administration delayed T1D, and adoptive splenocytes derived from ASD-administered donor NOD mice also delayed the onset of T1D in recipient NOD mice.
In our animal facility, the incidence of T1D in NOD mice is high at 90-100% and the percentages of peripheral CD4<sup>+</sup>Foxp3<sup>+</sup> cells in ~9-10-week-old female NOD mice are decreased compared to control (B6) mice shortly before high glucose is first detected (~12 weeks).
To address the role of PD-1 in the GC reaction in type 1 diabetes, we used tetramers to phenotype insulin-specific CD4<sup>+</sup> T and B cells in NOD mice.
In the present study we investigated further early changes in hepatic innate immunity and metabolism in two models of type 1 diabetes (T1D), the BBdp rat and NOD mouse.
Finally, we show that B cells in NOD mice express reduced PTEN, and low-dosage p110δ inhibitor therapy blocks disease progression in this model of type 1 diabetes.
In this study, T-cell PTPN2 deficiency in NOD mice markedly accelerated the onset and increased the incidence of type 1 diabetes as well as that of other disorders, including colitis and Sjögren syndrome.
Alterations of the integrity of the intestinal mucosa plays an important role in the pathogenesis of CD, and the NOD mouse model suggests an important role of a leaky intestinal epithelium in T1D as well.