Fig 1.
Delayed onset and reduced susceptibility to diabetes in paquinimod-treated NOD mice.
Incidence of diabetes in mice treated with different doses of paquinimod (mg/kg/day; n = 10 for each dose) or vehicle (Ctrl; n = 20) from 10 to 20w of age A) or 15 to 38 w of age B). In the experiment in C) and D) NOD mice were treated with 1mg/kg/day of paquinimod or vehicle starting at 15w of age and two groups of mice (treated n = 10; controls n = 10) were sacrificed after 5 weeks of treatment (20w of age) C), and two additional groups (treated n = 10; controls n = 10) were sacrificed after 15 weeks of treatment (30w of age). Incidence of diabetes in treated groups compared to the control group (**, p < 0.01, ***, p < 0.001, by Mann Whitney U test).
Fig 2.
Reduced insulitis in paquinimod treated NOD mice.
Cohorts of 15 w old mice were treated either with paquinimod (Paq; 1 mg/kg/day) or vehicle (Ctrl) as indicated. Groups of mice were sacrificed at the start of the experiment (Baseline n = 6), at 20 w of age (Ctrl n = 8; Paq n = 9) and at 30w of age (Ctrl n = 7; Paq n = 7). Serial sections of pancreatic tissue were prepared, stained with H&E and analyzed microscopically. A) Representative images are shown; scale bar in image: 100 μm. Insulitis scores B), and insulitis indexes C) are shown. In B), the extent of mononuclear cell infiltration was scored from 0 through 3. Score 0 (open bars), score 1 (light grey bars), score 2 (medium grey bars), score 3 (black bars). In C) insulitis index was calculated as described in Materials and Methods. Insulitis was scored by examining a minimum of 40 islets per animal. **, p < 0.01, ***, p < 0.001 by Mann Whitney U test.
Fig 3.
Paquinimod treatment reduces the frequency of Ly6Chi and F4/80+ cells in spleen of NOD mice.
Cells from spleen and panLN of the mice in Fig 1C and 1D were analyzed by flowcytometry. A), percentage of single CD19- CD11b+ cells out of total viable cells, as well as percentage of Ly6Chi inflammatory monocytes, Ly6G+ neutrophils, and SiglecF+ eosinophils among total CD11b+ cell population is shown both for B) spleens and C) pancreatic lymph nodes of mice. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, Mann–Whitney U test.