南方医科大学学报2026，Vol.46Issue(3)：541-549,9.DOI:10.12122/j.issn.1673-4254.2026.03.08
唾液链球菌胞外囊泡通过活化自然杀伤细胞加剧系统性红斑狼疮肾炎病理进展
Streptococcus salivarius-derived extracellular vesicles exacerbate progression of lupus nephritis by activating natural killer cells
摘要
Abstract
Objective To investigate the regulatory effects of Streptococcus salivarius-derived extracellular vesicles(SS-EVs)on natural killer(NK)cell activation and cytotoxic function and their role in progression of systemic lupus erythematosus(SLE).Methods Peripheral blood and fecal samples were collected from 35 SLE patients and 38 healthy individuals to assess the number and proportion of peripheral T cells,B cells,and NK cells.Fecal DNA was extracted for PCR amplification of S.salivarius DNA fragments and quantitative analysis using agarose gel electrophoresis.SS-EVs isolated by ultracentrifugation and characterized using transmission electron microscopy,nanoparticle tracking analysis,and Western blotting were co-cultured with NK cells,whose activation status and cytotoxicity were evaluated in vitro using qPCR and flow cytometry.Twenty-four MRL/lpr mice were randomized into 3 groups(n=8)for treatment with gavage of 100 μL PBS or 20 μg E.coli-EVs or SS-EVs in 100 μL PBS.Kidney pathology,immune complex deposition,and peripheral cytokine levels were assessed with HE staining,immunofluorescence staining,and ELISA.Results The number and proportion of peripheral NK cells were significantly reduced(P<0.0001)and the fecal abundance of S.salivarius was markedly increased in positive correlation with SLEDAI scores(R²=0.8369)in SLE patients.In vitro studies showed that SS-EVs significantly upregulated NK cell-activating receptors and enhanced NK-mediated cytotoxicity.In MRL/lpr mice,SS-EV treatment markedly exacerbated renal inflammation,promoted C3 and IgG immune complex deposition,and significantly increased serum levels of IL-6,TNF-α,IL-8,and CCL20.Conclusion S.salivarius is enriched in the gut of SLE patients and promotes NK-cell activation by releasing SS-EVs,which induce renal inflammation and immune complex deposition and contributes to SLE progression.S.salivarius and its EVs may represent novel therapeutic targets for treatment of SLE.关键词
系统性红斑狼疮/唾液链球菌/胞外囊泡/自然杀伤细胞/免疫调节Key words
systemic lupus erythematosus/Streptococcus salivarius/extracellular vesicles/natural killer cells/immunomodulation引用本文复制引用
肖洁,金凌岳,段丽娜,龚英,李海侠..唾液链球菌胞外囊泡通过活化自然杀伤细胞加剧系统性红斑狼疮肾炎病理进展[J].南方医科大学学报,2026,46(3):541-549,9.基金项目
国家自然科学基金(82002218,82202978) （82002218,82202978）
吴阶平医学基金资助项目(320.6750.2025-6-104)Supported by National Natural Science Foundation of China(82002218,82202978). （320.6750.2025-6-104）
