Figure 4. Loss of PTPN2 Promotes ASC-Dependent Inflammasome Activation.

(A) Colon pieces from WT and PTPN2-LysMCre mice with acute DSS colitis were analyzed by western blot for NLRP3, IL-1β, caspase-1, and IL-18 expression and maturation.

(B) BMDMs from WT and PTPN2-LysMCre mice were treated with indicated inflammasome activators and cell culture supernatants analyzed for IL-1β and IL-18 secretion.

(C) Serum samples from control (non-IBD) patients (n = 15) or CD patients homozygous either for the PTPN2 WT allele (PTPN2 TT, n = 8) or the CD-associated PTPN2 allele (PTPN2 CC, n = 8) were analyzed for presence of IL-1β and IL-18.

(D) Intestinal biopsies from non-inflamed and inflamed regions were taken from the same patients as in (C) and analyzed for IL1b and IL18 mRNA expression.

(E) BMDMs from WT, PTPN2-LysMCre, and ASC^–/– mice were left untreated or activated with MSU for 2 hr. ASC was precipitated and analyzed for tyrosine phosphorylation and co-precipitation of PTPN2.

Results are representative of at least two different experiments, each with three to five mice per group (A) or three or four biological replicates(B and E). Asterisks denote significant different results (*p < 0.05 and **p < 0.01; Student’s t test with Bonferroni correction). Error bars represent means ± SD. See also Figure S6.