P0190 Hypoglycemia induces SLC7A11-dependent disulfidptosis to regulate intestinal inflammation in IBD

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Abstract Background IBD is an autoimmune disease related to intestinal mucosal immune dysregulation, and cellular metabolism is an important factor affecting intestinal immunity[1]. Previous studies have shown that the low-glucose environment inhibits the intestinal immune response to IBD, and the specific mechanism is unknown. Recently, a new mode of cell death has been discovered in the study of tumor cells, which is cytotoxic death caused by cysteine accumulation in cells with high expression of SLC7A11 in a low-glucose environment[2]. Therefore, we wanted to explore whether the phenomenon of disulfidptosis with low glucose environmental effects also exists in IBD and whether it has an impact on the regulation of intestinal inflammation in IBD. Methods We intend to explore the role and mechanism of SLC7A11-dependent disulfidptosis in low-glucose environment in regulating intestinal inflammation in IBD through mass spectrometry, multi-omics and cryo-electron microscopy, and further explore the molecular mechanism of regulating SLC7A11 at the protein structure level, so as to provide a solid theoretical basis for exploring new cell death modes in different glucose environments in IBD. Results We found that the expression of SLC7A11 in the colon of IBD patients and mice with DSS-induced colitis increased, the glucose content of the intestinal mucosa increased, and the genes related to disulfidptosis were down-regulated, suggesting that there may be inhibition of disulfide death in the high-glucose environment in IBD. We further showed that the low-glucose environment may induce disulfidptosis and inhibit inflammation in macrophages under inflammatory conditions, suggesting that the hypoglucose environment may inhibit IBD inflammation by promoting disulfidptosis. Conclusion The hypoglycemic environment in IBD may induce slc7a11-dependent disulfidptosis, thereby inhibiting intestinal inflammation.