Core Insights - The research team at Zhejiang University has confirmed that defects in the human gene PLD4 can lead to systemic lupus erythematosus (SLE), providing a significant theoretical basis for precise diagnosis and treatment of the disease [1][2] - The study highlights the role of genetic factors and immune abnormalities in the development of SLE, identifying a single gene mutation as a contributing factor [1] - The findings were published in the international journal "Nature," marking a notable advancement in understanding the molecular mechanisms of SLE [1] Gene Defect and Mechanism - The research identified PLD4 gene defects in five patients with lupus nephritis through whole-exome sequencing, establishing a link between PLD4 and SLE for the first time [1] - PLD4 is highly expressed in dendritic cells, B cells, and monocytes, encoding a protein that degrades single-stranded nucleic acids in lysosomes [1] - Patients with PLD4 defects exhibited enhanced immune responses via the TLR7/TLR9 signaling pathway and increased levels of various inflammatory factors [1] Mouse Model and Treatment - To investigate the pathogenic mechanism of PLD4 gene defects, the research team created a mouse model with the same genetic deficiency, which displayed typical lupus-like phenotypes [2] - Kidney inflammation was notably significant in the deficient mice, aligning closely with the clinical renal phenotype observed in human patients [2] - Treatment with the JAK inhibitor Baricitinib significantly alleviated the lupus-like phenotype in deficient mice and effectively inhibited the overactivation of the type I interferon pathway in inflammatory cells derived from patients, suggesting a potential therapeutic strategy for SLE caused by PLD4 gene defects [2]