Supplementary Figure 4: Ifih1^R mice display enhanced triggering of autoimmune disease.

(a-b) Mice were injected with STZ for 4 days (55 mg/kg) and monitored for development of diabetes as described in Figure 5c. Tissues were harvested at week 15 post-STZ treatment for genotypes that developed disease [Ifih1^NR/NRPtpn22^NR/R (n=2) or Ifih1^NR/RPtpn22^NR/R (n=2)] and analyzed in a blinded fashion for histological changes. Scale bars equal 100 μm. (a) STZ treated heterozygous Ifih1^NR/NRPtpn22^NR/R mice. Both diabetic (A1, 20X) and nondiabetic (A2, 20X) animals had mild cellular changes evident in islets in H&E stained sections. Immuno-histochemical stains revealed reduced numbers of dark brown insulin positive cells in diabetics (B1, 20X) compared to nondiabetics (B2, 20X). Inflammation was rare and scant. (b) Compound heterozygous Ifih1^NR/RPtpn22^NR/R diabetic mice exhibited inflammatory changes in the pancreas with lesion severity ranging from scattered mild lymphocytic insulitis (arrow, C1, 40X) to atrophy and sclerosis with replacement by fibrous tissue containing pancreatic ductal remnants (arrows, C2, 10X). Immuno-histochemical staining for insulin and CD3 demonstrated atrophic and fibrosing pancreatitis containing whole or fragments of islets (arrows showing brown foci, D1, 20X) or CD3+ inflammatory cells (scattered brown foci, D2, 20X) dispersed among an isolated islet (arrow) and remnants of pancreatic ducts (stars). (b-c) BM12 CD4⁺ T cell were adoptively transferred into mice of indicated genotypes as described in Figure 5. Each dot represents results from an individual animal. (b) ELISAs for IgG anti-smRNP (upper panel) and IgG2c anti-smRNP (lower panel) autoantibodies at time points indicated. (c) Splenic cell numbers at week 15 post injection. Error bars represent ± SEM.