{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:16:09Z","timestamp":1790388969247,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100014219","name":"National Science Fund for Distinguished Young Scholars","doi-asserted-by":"publisher","award":["82025024"],"award-info":[{"award-number":["82025024"]}],"id":[{"id":"10.13039\/501100014219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82002218"],"award-info":[{"award-number":["82002218"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82202978"],"award-info":[{"award-number":["82202978"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Systemic lupus erythematosus (SLE) has been linked to gut microbiome dysbiosis, notably an overabundance of\n                    <jats:italic>Streptococcus anginosus<\/jats:italic>\n                    ; however, the impact of this microbial imbalance on disease pathogenesis remains unclear. Here, we investigated the contribution of\n                    <jats:italic>S. anginosus<\/jats:italic>\n                    \u2010derived extracellular vesicles (\n                    <jats:italic>SA<\/jats:italic>\n                    \u2010EVs) to SLE progression, with an emphasis on lupus nephritis (LN). Fifty\u2010four SLE patients and 43 healthy controls (HC) were recruited. The faecal, blood and serum samples from participants were collected. SLE disease activity (SLEDA) was evaluated by the SLEDA Index (SLEDAI). Stool\n                    <jats:italic>S. anginosus<\/jats:italic>\n                    abundance was quantified by quantitative PCR, NK cell activation by flow cytometry and serum proinflammatory cytokines profile by ELISA. Lupus\u2010prone MRL\/lpr mice were orally administered\n                    <jats:italic>SA<\/jats:italic>\n                    \u2010EVs to evaluate in vivo inflammatory responses, renal NK cell activation and renal histopathological changes.\n                    <jats:italic>S. anginosus<\/jats:italic>\n                    levels were significantly elevated in SLE patients relative to HC, positively correlated with SLEDAI scores and NK cell cytotoxicity. In vitro,\n                    <jats:italic>SA<\/jats:italic>\n                    \u2010EVs stimulation of patient NK cells significantly heightened proinflammatory mediator production (granzyme B, TNF\u2010\u03b1), increased cytotoxicity and downregulated inhibitory receptors (TIM\u20103, NKG2A, TIGIT) compared to control EVs from\n                    <jats:italic>S. Salivarius<\/jats:italic>\n                    (\n                    <jats:italic>SS<\/jats:italic>\n                    \u2010EVs). Mechanistically, lipoteichoic acid (LTA) within\n                    <jats:italic>SA<\/jats:italic>\n                    \u2010EVs engaged Toll\u2010like receptor 2 (TLR2) on NK cells, activating MyD88\/NF\u2010\u03baB signalling pathway. In MRL\/lpr mice,\n                    <jats:italic>SA<\/jats:italic>\n                    \u2010EVs treatment increased renal immune complex deposition, upregulated renal NK cell activation markers (NKp44, NKp46), and exacerbated LN pathology with greater immune cell infiltration and inflammatory cytokine levels. Furthermore, NK cell depletion with anti\u2010NK1.1 antibodies significantly prolonged survival in\n                    <jats:italic>SA<\/jats:italic>\n                    \u2010EVs administered mice. Thus,\n                    <jats:italic>SA<\/jats:italic>\n                    \u2010EVs exacerbate SLE by hyperactivating NK cells via the TLR2\u2010MyD88\u2010NF\u2010\u03baB pathway, leading to amplified systemic inflammation and aggravated LN. These findings underscore the potential of targeting\n                    <jats:italic>SA<\/jats:italic>\n                    \u2010EVs for therapeutic intervention in SLE.\n                  <\/jats:p>","DOI":"10.1002\/jev2.70134","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T14:19:28Z","timestamp":1752761968000},"source":"Crossref","is-referenced-by-count":16,"title":["Extracellular Vesicles Derived From\n                    <i>Streptococcus anginosus<\/i>\n                    Aggravate Lupus Nephritis by Triggering TLR2\u2010MyD88\u2010NF\u2010\u03baB Signalling in NK Cells"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5987-5344","authenticated-orcid":false,"given":"Ying","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Guangdong Provincial Key Laboratory of Precision Medical Diagnostics, Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Guangdong Provincial Key Laboratory of Single\u2010cell and Extracellular Vesicles, Nanfang Hospital Southern Medical University  Guangzhou P.R. China"},{"name":"Guangdong Provincial Clinical Research Center for Laboratory Medicine, Nanfang Hospital Southern Medical University  Guangzhou P.R. China"},{"name":"Department of Internal Medicine, Division of Hematology University of Maastricht  Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyue","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Guangdong Provincial Key Laboratory of Precision Medical Diagnostics, Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Guangdong Provincial Key Laboratory of Single\u2010cell and Extracellular Vesicles, Nanfang Hospital Southern Medical University  Guangzhou P.R. China"},{"name":"Guangdong Provincial Clinical Research Center for Laboratory Medicine, Nanfang Hospital Southern Medical University  Guangzhou P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2528-9239","authenticated-orcid":false,"given":"Lina","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Guangdong Provincial Key Laboratory of Precision Medical Diagnostics, Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Guangdong Provincial Key Laboratory of Single\u2010cell and Extracellular Vesicles, Nanfang Hospital Southern Medical University  Guangzhou P.R. China"},{"name":"Guangdong Provincial Clinical Research Center for Laboratory Medicine, Nanfang Hospital Southern Medical University  Guangzhou P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Guangdong Provincial Key Laboratory of Precision Medical Diagnostics, Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Guangdong Provincial Key Laboratory of Single\u2010cell and Extracellular Vesicles, Nanfang Hospital Southern Medical University  Guangzhou P.R. China"},{"name":"Guangdong Provincial Clinical Research Center for Laboratory Medicine, Nanfang Hospital Southern Medical University  Guangzhou P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Foshan Hospital of Traditional Chinese Medicine Guangzhou University of Chinese Medicine  Foshan P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HongXia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Guangdong Provincial Key Laboratory of Precision Medical Diagnostics, Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Guangdong Provincial Key Laboratory of Single\u2010cell and Extracellular Vesicles, Nanfang Hospital Southern Medical University  Guangzhou P.R. China"},{"name":"Guangdong Provincial Clinical Research Center for Laboratory Medicine, Nanfang Hospital Southern Medical University  Guangzhou P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Guangdong Provincial Key Laboratory of Precision Medical Diagnostics, Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Guangdong Provincial Key Laboratory of Single\u2010cell and Extracellular Vesicles, Nanfang Hospital Southern Medical University  Guangzhou P.R. China"},{"name":"Guangdong Provincial Clinical Research Center for Laboratory Medicine, Nanfang Hospital Southern Medical University  Guangzhou P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanying","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Guangdong Provincial Key Laboratory of Precision Medical Diagnostics, Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Guangdong Provincial Key Laboratory of Single\u2010cell and Extracellular Vesicles, Nanfang Hospital Southern Medical University  Guangzhou P.R. China"},{"name":"Guangdong Provincial Clinical Research Center for Laboratory Medicine, Nanfang Hospital Southern Medical University  Guangzhou P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Guangdong Provincial Key Laboratory of Precision Medical Diagnostics, Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Guangdong Provincial Key Laboratory of Single\u2010cell and Extracellular Vesicles, Nanfang Hospital Southern Medical University  Guangzhou P.R. China"},{"name":"Guangdong Provincial Clinical Research Center for Laboratory Medicine, Nanfang Hospital Southern Medical University  Guangzhou P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiufeng","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Guangdong Provincial Key Laboratory of Precision Medical Diagnostics, Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Guangdong Provincial Key Laboratory of Single\u2010cell and Extracellular Vesicles, Nanfang Hospital Southern Medical University  Guangzhou P.R. China"},{"name":"Guangdong Provincial Clinical Research Center for Laboratory Medicine, Nanfang Hospital Southern Medical University  Guangzhou P.R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yurong","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Guangdong Provincial Key Laboratory of Precision Medical Diagnostics, Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Guangdong Provincial Key Laboratory of Single\u2010cell and Extracellular Vesicles, Nanfang Hospital Southern Medical University  Guangzhou P.R. China"},{"name":"Guangdong Provincial Clinical Research Center for Laboratory Medicine, Nanfang Hospital Southern Medical University  Guangzhou P.R. China"},{"name":"Huayin Medical Laboratory Center Co., Ltd  Guangzhou P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weinan","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Nanfang Hospital Southern Medical University  Guangzhou P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2576-8780","authenticated-orcid":false,"given":"Lei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Guangdong Provincial Key Laboratory of Precision Medical Diagnostics, Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Guangdong Provincial Key Laboratory of Single\u2010cell and Extracellular Vesicles, Nanfang Hospital Southern Medical University  Guangzhou P.R. China"},{"name":"Guangdong Provincial Clinical Research Center for Laboratory Medicine, Nanfang Hospital Southern Medical University  Guangzhou P.R. China"},{"name":"State Key Laboratory of Multi\u2010organ Injury Prevention and Treatment, Nanfang Hospital Southern Medical University  Guangzhou P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8817-3218","authenticated-orcid":false,"given":"Haixia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Guangdong Provincial Key Laboratory of Precision Medical Diagnostics, Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Guangdong Provincial Key Laboratory of Single\u2010cell and Extracellular Vesicles, Nanfang Hospital Southern Medical University  Guangzhou P.R. China"},{"name":"Guangdong Provincial Clinical Research Center for Laboratory Medicine, Nanfang Hospital Southern Medical University  Guangzhou P.R. 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