{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T20:00:12Z","timestamp":1786132812250,"version":"build-2736575974"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","funder":[{"DOI":"10.13039\/spiddxci6rzy","name":"Capital's Funds for Health Improvement and Research","doi-asserted-by":"publisher","award":["2026-2-4079"],"award-info":[{"award-number":["2026-2-4079"]}],"id":[{"id":"10.13039\/spiddxci6rzy","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/sp4lxqwhdx6i","name":"National key research and development program","doi-asserted-by":"publisher","award":["2024YFC2510300\/2024YFC2510305"],"award-info":[{"award-number":["2024YFC2510300\/2024YFC2510305"]}],"id":[{"id":"10.13039\/sp4lxqwhdx6i","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/sp9epbj2srxf","name":"National Natural Science Fund","doi-asserted-by":"publisher","award":["82270754"],"award-info":[{"award-number":["82270754"]}],"id":[{"id":"10.13039\/sp9epbj2srxf","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/sp26euzo5vga","name":"Peking University Clinical Scientist Training Program","doi-asserted-by":"publisher","award":["BMU2024PYJH009"],"award-info":[{"award-number":["BMU2024PYJH009"]}],"id":[{"id":"10.13039\/sp26euzo5vga","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/sposvyj2ydfg","name":"Beijing Physician Scientist Training Project","doi-asserted-by":"publisher","award":["BJPSTP-2024-15"],"award-info":[{"award-number":["BJPSTP-2024-15"]}],"id":[{"id":"10.13039\/sposvyj2ydfg","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/spnilxvmr5xs","name":"National High Level Hospital Clinical Research Funding","doi-asserted-by":"publisher","award":["2025YC04"],"award-info":[{"award-number":["2025YC04"]}],"id":[{"id":"10.13039\/spnilxvmr5xs","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/spxub5htavlq","name":"National High Level Hospital Clinical Research Funding","doi-asserted-by":"publisher","award":["2024HQ01"],"award-info":[{"award-number":["2024HQ01"]}],"id":[{"id":"10.13039\/spxub5htavlq","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"abstract":"\n Key Points<\/jats:title>\n \n \n \n Canagliflozin ameliorated experimental ANCA-associated vasculitis through broad suppression of pathogenic T-cell subsets.<\/jats:p>\n <\/jats:list-item>\n \n The immunomodulatory effect of canagliflozin was mediated in part by inhibition of p38 mitogen-activated protein kinase signaling in T cells.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n The nephroprotective role of sodium-glucose cotransporter 2 (SGLT2) inhibitors has been well established by several randomized controlled trials involving patients with diabetic and nondiabetic CKD. However, the impact of SGLT2 inhibitors on ANCA-associated vasculitis (AAV) and the underlying mechanisms remain unclear.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n The therapeutic effects of canagliflozin were evaluated in a rat model of experimental AAV. RNA sequencing was performed on the kidney and lymph nodes. In parallel, mechanistic studies were conducted in mouse models. Myeloperoxidase-deficient (\n Mpo<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n ) mice were immunized with mouse myeloperoxidase and treated with canagliflozin. Splenocytes from these donors were then adoptively transferred into recombinase-activating gene-1\u2013deficient (\n Rag1<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n ) mice. Comprehensive immune phenotyping by flow cytometry, enzyme-linked immunospot assays, and\n in vitro<\/jats:italic>\n differentiation of human T cells were employed to dissect the immunomodulatory effects and underlying mechanisms.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Canagliflozin alleviated kidney injury, pulmonary hemorrhage, and T-lymphocyte infiltration in AAV rats. Renal transcriptomic analysis showed a suppression of adaptive immunity pathways. In the adoptive transfer model, canagliflozin treatment of donor mice led to a significant reduction in splenic Th1, Th17, and CD8\n +<\/jats:sup>\n T cells, accompanied by a markedly diminished capacity of splenocytes to secrete IFN-\n \u03b3<\/jats:italic>\n and IL-17A upon restimulation. Transfer of these modulated splenocytes conferred significant nephroprotection to recipient mice.\n In vitro<\/jats:italic>\n , canagliflozin suppressed the differentiation of primary CD4\n +<\/jats:sup>\n T cells from patients with AAV into both Th1 and Th17 lineages, but did not directly affect B-cell activation or antibody production. Mechanistically, canagliflozin inhibited the phosphorylation of both p38 and extracellular signal-regulated kinase mitogen-activated protein kinases in activated T cells, and the suppressive effect on cytokine production was partially reversed by activation of the p38 mitogen-activated protein kinase pathway.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Canagliflozin alleviated experimental AAV by suppressing pathogenic T cell effector responses\u2014an effect mechanistically linked to inhibition of the p38 signaling pathway.<\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.0000001137","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T16:00:26Z","timestamp":1779811226000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Canagliflozin Alleviates Experimental ANCA-Associated Vasculitis through Suppression of Pathogenic T-Cell Responses"],"prefix":"10.1681","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9749-8981","authenticated-orcid":false,"given":"Xiang-Yu","family":"Han","sequence":"first","affiliation":[{"name":"Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China"},{"name":"Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4720-2713","authenticated-orcid":false,"given":"Zhi-Ying","family":"Li","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China"},{"name":"Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1216-9693","authenticated-orcid":false,"given":"Su-Fang","family":"Chen","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China"},{"name":"Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Hui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China"},{"name":"Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6003-397X","authenticated-orcid":false,"given":"Mark A.","family":"Little","sequence":"additional","affiliation":[{"name":"Trinity Kidney Centre, Trinity Translational Medicine Institute, School of Medicine, Trinity College Dublin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6413-6973","authenticated-orcid":false,"given":"Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China"},{"name":"Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China"},{"name":"State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"issue":"10","key":"B1-20260716","doi-asserted-by":"crossref","first-page":"3452","DOI":"10.1002\/art.34562","article-title":"Classification of antineutrophil cytoplasmic autoantibody vasculitides: the role of antineutrophil cytoplasmic autoantibody specificity for myeloperoxidase or proteinase 3 in disease recognition and prognosis","volume":"64","author":"Lionaki","year":"2012","journal-title":"Arthritis Rheum."},{"issue":"1","key":"B2-20260716","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/art.37715","article-title":"2012 revised international Chapel Hill Consensus Conference nomenclature of 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