{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:18:41Z","timestamp":1783469921501,"version":"3.55.0"},"reference-count":60,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["4R00AI162843\u201004"],"award-info":[{"award-number":["4R00AI162843\u201004"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P01AI179405"],"award-info":[{"award-number":["P01AI179405"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015502","name":"Dialysis Clinics","doi-asserted-by":"publisher","award":["Paul Teschan Research Fund"],"award-info":[{"award-number":["Paul Teschan Research Fund"]}],"id":[{"id":"10.13039\/100015502","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["CDMRP\u2010LR240077: Award HT9425\u201025\u20101\u20100390("],"award-info":[{"award-number":["CDMRP\u2010LR240077: Award HT9425\u201025\u20101\u20100390("]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20GM152305"],"award-info":[{"award-number":["P20GM152305"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) that can lead to end\u2010stage kidney disease and increased mortality. IgG from patients with LN displays abnormal glycosylation, contributing to podocyte injury. CLEC7A (C\u2010type lectin domain family 7 member A) is a transmembrane lectin receptor that recognizes fucose on IgG. This study investigates the role of lectin\u2010glycan interactions in LN\u2010related podocyte dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>IgG isolated from patients with active LN and healthy controls was exposed to differentiated human podocytes. Gene and protein responses were assessed by quantitative polymerase chain reaction, Western blotting, immunofluorescence, phalloidin staining, calcium flux, and wound\u2010healing assays. Human kidney biopsies and MRL\/lpr mouse kidneys were examined to validate CLEC7A\u2013spleen tyrosine kinase (SYK) pathway activation and the glycan\u2010dependent effects of LN\u2010IgG.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Human podocytes exposed to the CLEC7A ligand curdlan or LN\u2010IgG, but not healthy control IgG or IgG from patients with SLE without nephritis, showed increased CLEC7A expression, impaired motility, cytoskeleton disruption, and reduced nephrin expression. Deglycosylation of LN\u2010IgG blocked CLEC7A binding and preserved podocyte function. Mechanistically, curdlan and LN\u2010IgG increased calcium flux and activated SYK. MRL\/\n                      <jats:italic>lpr<\/jats:italic>\n                      mice with nephritis exhibited elevated podocyte CLEC7A and SYK expression. Similarly, podocytes in kidney biopsies from patients with active LN exhibit increased expression of SYK and CLEC7A compared with healthy controls. Pharmacological SYK inhibition or CLEC7A silencing prevented podocyte injury.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We reveal a novel IgG lectin\u2010glycan\u2010CLEC7A\u2010SYK axis involved in the pathogenesis of LN, which can be targeted therapeutically in patients with LN.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art70260-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70260","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T12:07:16Z","timestamp":1782130036000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>IgG<\/scp>\n                    Glycosylation\u2010Dependent\n                    <scp>CLEC7A<\/scp>\n                    Signaling Drives Podocyte Dysfunction in Lupus Nephritis"],"prefix":"10.1002","author":[{"given":"Rohit","family":"Upadhyay","sequence":"first","affiliation":[{"name":"John W. Deming Department of Medicine, Section of Nephrology &amp; Hypertension Tulane University School of Medicine  New Orleans Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexia","family":"Orellana","sequence":"additional","affiliation":[{"name":"John W. Deming Department of Medicine, Section of Nephrology &amp; Hypertension Tulane University School of Medicine  New Orleans Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9589-2360","authenticated-orcid":false,"given":"George C.","family":"Tsokos","sequence":"additional","affiliation":[{"name":"Department of Medicine Beth Israel Deaconess Medical Center, Harvard Medical School  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2899-6758","authenticated-orcid":false,"given":"Rhea","family":"Bhargava","sequence":"additional","affiliation":[{"name":"John W. Deming Department of Medicine, Section of Nephrology &amp; Hypertension Tulane University School of Medicine  New Orleans Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0141-9"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12882-022-02846-z"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfs073"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2016.05.017"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2023.13091"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.147789"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2025.110427"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI99507"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/82_2019_152"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01886-1"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-015-0450-1"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210665200"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2011.08.031"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201911875"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.137191"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.17451"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1103031"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.812148"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2009.00793.x"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00242-0"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2002.00114.x"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.454405"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(97)80106-9"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4613-4220-5_14"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1998.tb01238.x"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(99)01574-1"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M004549200"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00868.x"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2024.110180"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-49684-z"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00184.2016"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1335936"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-13-8871-2_10"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-0196-7"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5000410"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.604961"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2018.05.003"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M111.010090"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3401"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2021.102804"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.818382"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwz085"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2009.01.003"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.334"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010863"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-023-01074-1"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2022.10.019"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2020101525"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00964.x"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2012.06.003"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.11.8145"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2007.06.005"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3198"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27452"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00198.2010"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00026.2012"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2021.108795"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2020.100137"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25125"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.70260","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/art.70260","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.70260","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.70260"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,7]]},"references-count":60,"alternative-id":["10.1002\/art.70260"],"URL":"https:\/\/doi.org\/10.1002\/art.70260","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,7]]},"assertion":[{"value":"2025-12-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"art.70260"}}