{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:39:47Z","timestamp":1791268787298,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,9,22]],"date-time":"2015-09-22T00:00:00Z","timestamp":1442880000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Health and Medical Research Council of Australia"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2016,1]]},"abstract":"Abstract<\/jats:title>\n \n Antibody\u2010dependent activation of myeloid cells within the glomerulus plays a central role in rapidly progressive forms of glomerulonephritis. The spleen tyrosine kinase (Syk) is expressed by all leukocytes, except mature T cells, and is required for signalling via the B\u2010cell receptor, Fc receptors, and some integrins. Syk has been proposed as a therapeutic target in glomerulonephritis. However, little is known of Syk activation in human kidney disease, while studies in experimental glomerulonephritis using non\u2010selective Syk inhibitors require validation via conditional gene deletion. The current study addressed both of these important points. Syk activation (Tyr\n 525\/526<\/jats:sup>\n phosphorylation) was examined in a cohort of 96 patients with different glomerulonephritides. Syk activation was evident in infiltrating leukocytes, mainly neutrophils and macrophages, in 36\/40 cases of rapidly progressive glomerulonephritis. In contrast, non\u2010proliferative diseases showed little or no Syk activation. Glomerular and interstitial cells exhibiting Syk activation correlated with renal function and systemic inflammation. Next, we examined mice with conditional\n Syk<\/jats:italic>\n gene deletion in myeloid cells (\n \n \n Syk\n My<\/jats:sup>\n <\/jats:styled-content>\n <\/jats:italic>\n ) versus\n \n Syk\n f\/f<\/jats:sup>\n <\/jats:italic>\n littermate controls in nephrotoxic serum nephritis\u00a0\u2013\u00a0a model of rapidly progressive glomerulonephritis. Control\n \n Syk\n f\/f<\/jats:sup>\n <\/jats:italic>\n mice featured a transient neutrophil influx at 3 h and severe disease on day 9 of nephrotoxic serum nephritis, with crescent formation, macrophage infiltration, inflammation, kidney fibrosis, and renal dysfunction. In contrast,\n \n \n Syk\n My<\/jats:sup>\n <\/jats:styled-content>\n <\/jats:italic>\n mice had significantly reduced neutrophil and macrophage infiltration despite equivalent glomerular deposition of humoral reactants.\n \n \n Syk\n My<\/jats:sup>\n <\/jats:styled-content>\n <\/jats:italic>\n mice exhibited reduced crescent formation, inflammation, and fibrosis, with improved renal function on day 9 of nephrotoxic serum nephritis. In conclusion, Syk activation is prominent in infiltrating myeloid cells in human rapidly progressive glomerulonephritis, and functional studies demonstrate that\n Syk<\/jats:italic>\n deletion in myeloid cells is protective in mouse nephrotoxic serum nephritis. Copyright \u00a9 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.\n <\/jats:p>","DOI":"10.1002\/path.4598","type":"journal-article","created":{"date-parts":[[2015,8,6]],"date-time":"2015-08-06T13:42:54Z","timestamp":1438868574000},"page":"10-20","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Myeloid cell\u2010mediated renal injury in rapidly progressive glomerulonephritis depends upon spleen tyrosine kinase"],"prefix":"10.1002","volume":"238","author":[{"given":"Jessica","family":"Ryan","sequence":"first","affiliation":[{"name":"Department of Nephrology Monash Medical Centre, Monash Health Clayton Victoria Australia"},{"name":"Monash University Department of Medicine Monash Medical Centre Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank Y","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Nephrology Monash Medical Centre, Monash Health Clayton Victoria Australia"},{"name":"Monash University Department of Medicine Monash Medical Centre Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjie","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Nephrology Monash Medical Centre, Monash Health Clayton Victoria Australia"},{"name":"Monash University Department of Medicine Monash Medical Centre Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elyce","family":"Ozols","sequence":"additional","affiliation":[{"name":"Department of Nephrology Monash Medical Centre, Monash Health Clayton Victoria Australia"},{"name":"Monash University Department of Medicine Monash Medical Centre Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Kanellis","sequence":"additional","affiliation":[{"name":"Department of Nephrology Monash Medical Centre, Monash Health Clayton Victoria Australia"},{"name":"Monash University Department of Medicine Monash Medical Centre Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg H","family":"Tesch","sequence":"additional","affiliation":[{"name":"Department of Nephrology Monash Medical Centre, Monash Health Clayton Victoria Australia"},{"name":"Monash University Department of Medicine Monash Medical Centre Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J","family":"Nikolic\u2010Paterson","sequence":"additional","affiliation":[{"name":"Department of Nephrology Monash Medical Centre, Monash Health Clayton Victoria Australia"},{"name":"Monash University Department of Medicine Monash Medical Centre Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,9,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2765"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2013.06.034"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a002970"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.5788"},{"key":"e_1_2_7_6_1","first-page":"1511","volume-title":"Diseases of the Kidney and Urinary Tract","author":"Kerr PG","year":"2007"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5000212"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/16.8.1638"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1998.00978.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2011.61"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI3256"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2000.00364.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.11.1853"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2015.29"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23428"},{"key":"e_1_2_7_16_1","doi-asserted-by":"crossref","first-page":"2086","DOI":"10.1002\/art.27452","article-title":"Suppression of skin and kidney disease by inhibition of spleen tyrosine kinase in lupus\u2010prone mice","volume":"62","author":"Deng GM","year":"2010","journal-title":"Arthritis Rheum"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013090978"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1358\/dof.2011.036.04.1588554"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2011.137"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009030263"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.109058"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm500228a"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1990"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni893"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012111094"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/43.1.7822770"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1797.2012.01567.x"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102603"},{"key":"e_1_2_7_29_1","first-page":"2595","article-title":"Critical role for the tyrosine kinase Syk in signalling through the high affinity IgE receptor of mast cells","volume":"13","author":"Costello PS","year":"1996","journal-title":"Oncogene"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.7.1027"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.7.4209"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-08-044669"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.04.013"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)61209-6"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00389.2012"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201141502"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.9.2333"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113720"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5002404"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2009.2"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000082"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI6710"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005091013"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.4598","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.4598","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T14:20:52Z","timestamp":1760970052000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.4598"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9,22]]},"references-count":42,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,1]]}},"alternative-id":["10.1002\/path.4598"],"URL":"https:\/\/doi.org\/10.1002\/path.4598","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,9,22]]},"assertion":[{"value":"2015-06-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-08-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-09-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}