浙江大学最新Nature论文：发现系统性红斑狼疮新型致病基因突变——PLD4

Core Viewpoint - The research identifies loss-of-function mutations in the PLD4 gene as a cause of systemic lupus erythematosus (SLE), providing a theoretical basis for precise diagnosis and treatment of the disease [3][10]. Group 1: Research Findings - The study published in Nature confirms that mutations in the PLD4 gene can lead to SLE and elucidates the pathogenic mechanism involved [3]. - The research team reported five SLE patients with renal lesions exhibiting PLD4 biallelic mutations [8]. - PLD4 is highly expressed in dendritic cells, monocytes, and B cells, and functions as a 5' nucleic acid exonuclease that limits the overactivation of TLR7 and TLR9 [7]. Group 2: Mechanism of Action - TLR7 and TLR9 play critical roles in sensing RNA and DNA, initiating downstream inflammatory signaling pathways that contribute to SLE development [6]. - The absence of PLD4 leads to excessive activation of TLR7 and TLR9, resulting in heightened inflammatory responses and the production of autoantibodies [10]. Group 3: Potential Therapeutic Implications - PLD4-deficient mice exhibited autoimmune phenotypes and responded to the JAK inhibitor baricitinib, suggesting that targeting type I interferon may be a potential therapy for SLE patients with PLD4 deficiency [10].