Fig. 8

Increasing γδT cells infiltration, IFN-γ response and pyroptosis were triggered by gluten. A The comparison of PES, response to IFN-γ pathway, γδT cells infiltration degree, expression level of GSDMD and IRF1 between gluten free diet (GFD) patients and post gluten challenge (PGC) patients in dataset GSE145358. B The comparison of γδT cells-derived IFNG expression level among HCs, active CeD patients and GFD patients in dataset GSE123649. C Western blotting showed the expression level of GSDMD-FL, GSDMD-C, Pro-caspase-1, Cleaved caspase-1, IL-1β and β-tublin in CeD or HC animal duodenal tissues. D Western blotting showed the expression level of GSDMD-FL, GSDMD-C, Cleaved caspase-1, IL-1β and β-tublin in Caco-2 cell line treated with IFN-γ (50 ng/ml) and/or Pepsin-trypsin gliadin (PTG) (200 μg/ml). E Concentration of IL-1β in the supernatant of Caco-2 cell treated with IFN-γ (50 ng/ml) and/or Pepsin-trypsin gliadin (PTG) (200 μg/ml) was measured by ELISA. F Cell viability in Caco-2 cell treated with IFN-γ (50 ng/ml) and/or Pepsin-trypsin gliadin (PTG) (200 μg/ml) was measured by CCK-8 assay. G Hypothetical mechanism of γδT cells mediating pyroptosis in CeD pathogenesis. Patients with a genetic predisposition to CeD could not completely digest gluten.The intermediate products were taken up by antigen-presenting cells and then transferred to the lymphocytes. Upon stimulation, γδT cells produced a large amount of IFN-γ, which upregulate the expression of GSDMD in epithelial cells via IFN-γ/IRF1/GSMDM axis, led epithelial cells to be in a “pre-pyroptotic” condition. Then, epithelia pyroptosis were triggered by PTG/Caspase-1/GSDMD/IL-1β pathway, resulting in a programmed cell death and the release of inflammatory mediators, leding to duodenal villi atrophy and malabsorption of nutrients