Fig. 2: Induction of TET2 in human β cells with inflammation.

a Expression of TET2 protein in human β cells in vivo in pancreas from a healthy control subject (a), patient with autoimmune pancreatitis (b), a nondiabetic individual with autoantibodies to GADA and ZnT8 who is a relative of a patient with Type 1 diabetes (c), a patient with recent-onset T1D (d), patient with Type 1 diabetes for 15 years without detectable autoantibodies (e), and (f) a patient with chronic pancreatitis. The sections were stained with anti-TET2 (red) and anti-insulin (green) as well as anti-CD45 (Cyan) antibody. DAPI (blue) stains the cell nucleus. The merged staining is shown. Arrows indicate TET2 + β cells in b, c, and d and β cells in e and f. Data were from normal individuals (n = 8), donors with autoimmune pancreatitis (n = 5), nondiabetic donors who were autoantibody+ (n = 7), and C-peptide + patients with T1D of relatively short duration (n = 7). Scale bars: 25 μm. b Image J quantification of the fluorescence intensity of TET2 staining in islets studied in Fig. 1a. Twenty islets per condition were looked at, with three–seven donors for each condition. Different clinical conditions were compared to a healthy individual. Statistical analysis was performed using one-way ANOVA with Dunnett’s multiple comparisons test. c Human islets were cultured with individual or combined cytokines as indicated for 24 h before transcription analysis of TET2 gene by qRT-PCR. The fold of TET2 mRNA induced by cytokines relative to islets cultured in media alone is shown. Data were mean ± SD from five experiments, each with 2000–8000 islet equivalents (IEQ) from nondiabetic individuals (Fold vs islets cultured in media alone. Statistical analysis was performed using one-way ANOVA with Dunnett’s multiple comparisons test.