Figure 4
Innate immune responses to EV infection in the islets of SPIDDM pancreases. (a–c) MDA5 (a) and VP1/2Apro (b) expression of SPIDDM islets. Merged image (c) shows MDA5 expression in the islets. The expression of MDA5 (brown) is lost around some cells, which express 2Apro (red) as shown by the arrows. (d–f) IFN-β1 (d), VP1/2Apro (e) expression of SPIDDM islets. Merged image (f) shows the expression of IFN-β1 (brown) is lost around some cells, which express 2Apro as indicated by the arrows. (g,j) Double immunostaining for 2Apro (red, g,j) and MDA5 (g, brown) or IFN-β1 (j, brown) show that where 2Apro (red) was present in and around islet cells, MDA5 or IFN-β1 area was lost (arrows). (h) The MDA5-positive cell area relative to the islet area as related to the duration of diabetes (p < 0.0001, R2 = 0.393, n = 167). The solid curve depicts an exponential decay function of the diabetes duration (Y): AF_MDA5 = a EXP (b Y), where AF_MDA5 is the fractional area of MDA5-positive cells, which was square-root transformed to suppress heterogeneity of variances among the durations and also improve fitting to normal distribution for each duration. The coefficients were estimated at a = 57.9 (%) and b = −0.135 (p < 0.0001; 95% CI [−0.161, −0.109]). Also shown are 95% confidence boundaries (dashed curves) of the exponential function. (k) Temporal change of the IFN-β1-positive cell area relative to the islet area across the duration of diabetes (p < 0.0001, R2 = 0.446, n = 122). The solid curve depicts an exponential decay function of the diabetes duration (Y): AF_ IFN-β1 = a EXP (b Y), where AF_ IFN-β1 is the fractional area of IFN-β1-positive cells, which was square-root transformed to suppress heterogeneity of variances among the durations and improve fitting to normal distribution at each duration. The coefficients were estimated at a = 42.0 (%) and b = −0.108 (p < 0.0001; 95% CI [−0.129, −0.085]). Also shown are 95% confidence boundaries (dashed curves) of the exponential function. (i,l) Expression of MDA5 and IFN-β1 in the islets of SPIDDM was decreased compared with VP1-positive non-DC.
