We conclude that treatment of NOD mice with an antibody against CSF-1 receptor reduced diabetes incidence and led to the development of a regulatory pathway that controlled autoimmune progression.
Finally, EPA feeding improved glucose tolerance and β-cell function in a mouse model of diabetes that incorporates a strong immune phenotype: the NOD mouse.
At this time, NOD mice in the control arm were treated with LinBit insulin pellets and randomised to bi-weekly therapeutic injections of either PBS or IL-22 (200 ng/g) and followed until overt diabetes was diagnosed, as defined above.
The expansion of the Vα/Vβ species associated with diabetes depends upon CD40 signalling; NOD.CD154<sup>-/-</sup> mice do not expand the same TCR species.
Pancreatic IL-2Rβ<sup>Y3</sup> T<sub>regs</sub> showed impaired development into IL-10-secreting effector T<sub>regs</sub> The pancreatic lymph nodes and pancreases of NOD-Y3 mice had increased numbers of antigen-experienced CD4<sup>+</sup> effector T cells, which was largely due to impaired T<sub>regs</sub>, because adoptively transferred pancreatic autoantigen-specific CD4<sup>+</sup> Foxp3<sup>-</sup> T cells from NOD-Y3 mice did not accelerate diabetes in NOD.SCID recipients.
In this issue of Diabetologia Grönholm et al (DOI: 10.1007/s00125-017-4276-5 ) report that parenteral administration of the same insulin analogue has no preventive effect whatsoever on the development of diabetes in NOD mice; in fact, high doses of the metabolically inactive insulin accelerated disease development.
Tolerizing vaccination of NOD mice with a cDNA plasmid expressing full-length proinsulin prevented diabetes, whereas plasmids encoding ZnT8 and DβH did not.
In the resulting 3A9 TCR:iHEL NOD.H2(k)-Chr12 mice, we observed a significant decrease in diabetes incidence as well as a decrease in both the quantity and affinity of HEL-specific IgG autoantibodies relative to 3A9 TCR:iHEL NOD.H2(k) mice.
We explored TIM4 expression and targeting in Th1 (BALB/c islets into C57BL/6 mice) and Th2 (BALB/c islets into Tbet(-/-) C57BL/6 mice) models of anti-islet alloimmune response and in a model of anti-islet autoimmune response (diabetes onset in NOD mice).
Recent in vitro and animal studies show that APC's strong anti-inflammatory and anti-apoptotic properties are beneficial in preventing β-cell destruction and diabetes in the NOD mouse model of type 1 diabetes.
Despite the well known role of nucleotide oligomerization domain (NOD) receptor proteins in innate immunity, their association with diabetes is less explored.
Thioredoxin-interacting protein (TXNIP), a regulator of cellular oxidative stress, has been associated with activation of NOD-like receptor 3 (NLRP3) inflammasome, inflammation and lipid metabolism, suggesting it has a role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) in diabetes.
Expression of the spliced variant (Adora1-Var) was upregulated in the pancreas of 12-week-old NOD versus age-matched NOD.B10 (non-diabetes-susceptible) control mice and was detected in the pancreas of AA(+) patients but not in control subjects or overtly diabetic patients, suggesting that inflammation drives the splicing of Adora1.
We show that combination therapy with low-dose systemic anti-CD3 stably reverted diabetes in NOD mice and increased frequencies of local Tregs, which not only accumulated in the pancreatic islets, but also suppressed immune response in an autoantigen-specific way.