Figure 1. β-cell-specific expression of IL-35 at a late preclinical stage prevents the onset of diabetes.

12 week-old NOD female mice were treated with AAV8mIP-IL35, AAV8mIP-GFP, or left untreated. (A) Ebi3 and Il12α mRNA levels in pancreases/islets were compared between AAV8mIP-IL35 and untreated cohorts; the ratio of expression for the respective genes between AAV8mIP-IL35 and untreated controls is depicted. Data represent average ± SEM of 2 independent experiments in which pancreas/islets were pooled from 2–3 mice per cohort in each experiment. ***p<0.001 (Student’s t test). (B) Cohorts treated with AAV8mIP-IL35 (10×10¹⁰ vp, n=14; 2.5×10¹⁰ vp, n=5), AAV8mIP-GFP (10×10¹⁰ vp, n=10), or left untreated (n=10) were monitored for overt diabetes by blood glucose levels. **p<0.01, ***p<0.001 (Kaplan-Meier log-rank test). (C) Insulitis was determined in hematoxylin and eosin stained pancreatic sections of 35-week old non-diabetic NOD female mice treated with AAV8mIP-IL35 (n=6) and compared to 12-week old NOD female mice (n=8). Insulitis was scored as the percentage of islets with no insulitis, peri-insulitis, <50% intra-insulitis, and >50% intra-insulitis. Data shown as average + SEM of the indicated number of mice pooled from 2 experiments.