MedComm丨IF：10.7丨系统性红斑狼疮患者肠道释放的脂多糖通过Casp11-GSDMD激活巨噬细胞的焦亡

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Chestnut Studying       摘要  Noncanonical pyroptosis is triggered by Caspase 4/5/11, which cleaves Gasdermin D (GSDMD), leading to cell lysis. While GSDMD has been studied previously in systemic lupus erythematosus (SLE), the role of pyroptosis in SLE pathogenesis remains unclear and contentious, with limited understanding of Caspase 11-mediated pyroptosis in this condition. In this study, we explored the level of Caspase 11-mediated pyroptosis in SLE, identifying both the upstream pathways and the interaction between pyroptosis and adaptive immune responses. We observed increased Caspase 5/11 and GSDMD-dependent pyroptosis in the macrophages/monocytes of both lupus patients and mice. We identified serum lipopolysaccharide (LPS), released from the gut due to a compromised gut barrier, as the signal that triggers Caspase 11 activation in MRL/lpr mice. We further discovered that pyroptotic macrophages promote the differentiation of mature B cells independently of T cells. Additio ………………………………