Fig. 6.

Treatment of Tlr9^+/+ NOD mice with TLR9 antagonist recapitulated Tlr9^−/− phenotypes in vivo. (a) Treatment with TLR9 antagonist enhances CD140a expression on islet beta cells from Tlr9^+/+ NOD mice. CD140a expression on islet beta cells from the female progeny (5–6 weeks old) of TLR9 antagonist ODN- or control (Ctrl) ODN-treated pregnant NOD mice (p = 0.0095; n = 7 mice for both groups). (b) TLR9 antagonist treatment increases beta cell number. Number of beta cells/mouse in the female progeny (5–6 weeks old) of TLR9 antagonist ODN- or Ctrl ODN-treated pregnant NOD mice (p = 0.044; n = 6 mice for both groups). (c) TLR9 antagonist treatment enhances beta cell function. Insulin release from islets from the female progeny (5–6 weeks old) of TLR9 antagonist ODN- (black circles) or Ctrl ODN-treated (white circles) pregnant NOD mice (p = 0.0007; n = 6 mice for both groups). (d) TLR9 antagonist treatment prevents spontaneous type 1 diabetes development. Pregnant NOD mice (n = 3) were treated with TLR9 antagonist ODN and the incidence of diabetes was monitored in the female progeny (p = 0.019) (black circles; n = 10 mice) or Ctrl ODN (white circles, n = 7 mice). Two independent experiments were performed in (a–c), n = 3–4 mice per group per experiment. Data were analysed in (a, b) by two-tailed unpaired Student’s t test, in (c) by two-way ANOVA and in (d) by logrank test for survival. Data are expressed in (a) and (b) as means (horizontal line) and in (c) as means (SD). *p < 0.05, **p < 0.01, ***p < 0.001