{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:07:44Z","timestamp":1791220064636,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2010,3,10]],"date-time":"2010-03-10T00:00:00Z","timestamp":1268179200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis & Rheumatism"],"published-print":{"date-parts":[[2010,7]]},"abstract":"Abstract<\/jats:title>\n \n Objective<\/jats:title>\n \n Spleen tyrosine kinase (Syk) is involved in membrane\u2010mediated signaling in various cells, including immune cells. It is overexpressed in T cells from patients with systemic lupus erythematosus (SLE), and its inhibition has been shown to improve T cell function as well as to improve disease manifestations in (NZB \u00d7 NZW)F\n 1<\/jats:sub>\n lupus\u2010prone mice and in patients with rheumatoid arthritis. While clinical trials examining Syk inhibition in patients with SLE are being considered, the aim of our experiments was to determine whether the therapeutic effects of Syk inhibition extend to other strains of lupus\u2010prone mice and whether they result in improvement in skin disease and modification of established disease.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Female MRL\/\n lpr<\/jats:italic>\n or BAK\/BAX mice were studied. Starting either at age 4 weeks (before disease) or at age 16 weeks (after established disease) and continuing for up to 16 weeks, mice were fed chow containing the Syk inhibitor R788 or control chow.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We found that inhibition of Syk in MRL\/\n lpr<\/jats:italic>\n and BAK\/BAX mice prevented the development of skin disease and significantly reduced established skin disease. Similarly, Syk inhibition reduced the size of the spleen and lymph nodes, suppressed the development of renal disease, and suppressed established renal disease. Discontinuation of treatment resulted in extended suppression of skin disease for at least 8 weeks and suppression of renal disease for 4 weeks.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Syk inhibition suppresses the development of lupus skin and kidney disease in lupus\u2010prone mice, suppresses established disease in lupus\u2010prone mice, and may represent a valuable treatment for patients with SLE.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/art.27452","type":"journal-article","created":{"date-parts":[[2010,3,10]],"date-time":"2010-03-10T13:14:54Z","timestamp":1268226894000},"page":"2086-2092","source":"Crossref","is-referenced-by-count":139,"title":["Suppression of skin and kidney disease by inhibition of spleen tyrosine kinase in lupus\u2010prone mice"],"prefix":"10.1002","volume":"62","author":[{"given":"Guo\u2010Min","family":"Deng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances Rena","family":"Bahjat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polly R.","family":"Pine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George C.","family":"Tsokos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,6,29]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.5.1725"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1460"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/378303a0"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/380634a0"},{"key":"e_1_2_6_6_2","doi-asserted-by":"crossref","first-page":"5429","DOI":"10.4049\/jimmunol.152.11.5429","article-title":"Stimulation of macrophage Fc\u03b3RIIIA activates the receptor\u2010associated protein tyrosine kinase Syk and induces phosphorylation of multiple proteins including p95Vav and p62\/GAP\u2010associated protein","volume":"152","author":"Darby C","year":"1994","journal-title":"J 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