Fig. 4: Inflammation in IgG4-RD patients is mediated via the IL-1β inflammasome axis.

A–D Masson staining of pancreatic (B, n = 4), kidney (C, n = 5), and liver (D, n = 5) tissues and the percentage of the fibrotic area from WT and Usp25 KO mice (scale bar = 100 μm). Shown are representative dot plots (A). E IL-13 levels in the serum of Usp25 KO and WT mice were quantified by ELISA (n = 15). F, G Purified B cells from HCs and IgG4-RD patients were pre-incubated with 25 μM of MG132 at 37 °C for 30 min and then stimulated in the same way as in (Fig. 2G) except stained for pSMAD3 and nuclei using DAPI (scale bar = 2.5 μm) and shown are representative images captured using confocal (F). The MFI of pSMAD3 was analyzed (G). H Western blots of pSMAD3, SMAD3, COL1A1, and fibronectin (FN) in PBMCs of IgG4-RD patients and HCs stimulated with sAg for designated times. I Immunoblot showing the levels of TRAF6, caspase-1, NLRP3, and IL-1β in PBMCs from HCs and IgG4-RD patients. J Western blots of pNF-κB, pIKKB, NF-κB, and IKKB in PBMCs from HCs and IgG4-RD patients stimulated with sAg for designated times. K IL-1β levels in the serum of Usp25 KO and WT mice were quantified by ELISA (n = 13). L, M H&E staining results of lung tissues from WT and Usp25 KO mice (L) and western blot analysis of the levels of caspase-1, NLRP3, and IL-1β in B cells from WT and Usp25 KO mice (M) after being injected (i.p.) with 10 mg/kg of LPS for 24 h (Scale bar, 200 μm). All images were representative images from 3 independent experiments. Data points in (B, C, D, E, G, and K) are represented as Mean ± SED. Statistical significance was based on two-tailed unpaired Student’s t-test. Relevant p values are given in the graph. *P < 0.05; **P < 0.01; ***P < 0.001. Source data are provided as a Source Data file.