Figure 6.

Gene expression of Padi citrullinating enzymes in murine mTECs and islets. A, C, and D: RT-qPCR expression (mean ± SD) of Padi2 in islets from 6-week-old and 10-week-old mice (A) and of Padi2 (C) and Padi4 (D) in mTECs from 6- to 8-week-old C57BL/6 and NOD mice; *P ≤ 0.03, **P ≤ 0.005, ***P < 0.001 by one-way ANOVA. B: Padi enzymatic activity (mean ± SD) in whole pancreata and thymi of 6-week-old C57BL/6 and NOD mice; ***P < 0.001 by Student t test. E: Expression (median ± range) of Padi isoforms in WT and Aire^−/− C57BL/6 mice. Murine mature MHC-II^high mTECs were prepared from 4- to 6-week-old mice (n = 3/each) and analyzed by RNAseq; *P ≤ 0.03, **P ≤ 0.003, ***P < 0.001 by Welch t test. F: Enrichment of PTM enzyme gene sets in MHC-II^high mTECs from WT vs. Aire^−/− mice. Red lines indicate the 0.01 family-wise error rate P (P_FWER) cutoff value for statistical significance (for citrullination, P_FWER = 0.0016, corresponding to a WT-normalized enrichment score of 2.4). ROS, reactive oxygen species; RPKM, reads per kilobase per million mapped reads; wks, weeks.