{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T20:14:55Z","timestamp":1792872895844,"version":"4.5.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2005,9,1]],"date-time":"2005-09-01T00:00:00Z","timestamp":1125532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>T cells isolated from patients with systemic lupus erythematosus (SLE) express low levels of CD3\u03b6-chain, a critical molecule involved in TCR-mediated signaling, but the involved mechanisms are not fully understood. In this study we examined caspase-3 as a candidate for cleaving CD3\u03b6 in SLE T cells. We demonstrate that SLE T cells display increased expression and activity of caspase-3. Treatment of SLE T cells with the caspase-3 inhibitor Z-Asp-Glu-Val-Asp-FMK reduced proteolysis of CD3\u03b6 and enhanced its expression. In addition, Z-Asp-Glu-Val-Asp-FMK treatment increased the association of CD3\u03b6 with lipid rafts and simultaneously reversed the abnormal lipid raft preclustering, heightened TCR-induced calcium responses, and reduced the expression of FcR\u03b3-chain exclusively in SLE T cells. We conclude that caspase-3 inhibitors can normalize SLE T cell function by limiting the excessive digestion of CD3\u03b6-chain and suggest that such molecules can be considered in the treatment of this disease.<\/jats:p>","DOI":"10.4049\/jimmunol.175.5.3417","type":"journal-article","created":{"date-parts":[[2014,4,24]],"date-time":"2014-04-24T13:44:04Z","timestamp":1398347044000},"page":"3417-3423","source":"Crossref","is-referenced-by-count":56,"title":["Increased Caspase-3 Expression and Activity Contribute to Reduced CD3\u03b6 Expression in Systemic Lupus Erythematosus T Cells"],"prefix":"10.1093","volume":"175","author":[{"given":"Sandeep","family":"Krishnan","sequence":"first","affiliation":[{"name":"Department of Cellular Injury, Walter Reed Army Institute of Research , Silver Spring, MD 20910"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliann G","family":"Kiang","sequence":"additional","affiliation":[{"name":"Department of Cellular Injury, Walter Reed Army Institute of Research , Silver Spring, MD 20910"},{"name":"Department of Medicine, Uniformed Services University of the Health Sciences , Bethesda, MD 20814"},{"name":"Department of Pharmacology, Uniformed Services University of the Health Sciences , Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn U","family":"Fisher","sequence":"additional","affiliation":[{"name":"Department of Cellular Injury, Walter Reed Army Institute of Research , Silver Spring, MD 20910"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhusoodana P","family":"Nambiar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Walter Reed Army Institute of Research , Silver Spring, MD 20910"},{"name":"Department of Medicine, Uniformed Services University of the Health Sciences , Bethesda, MD 20814"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang T","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Cellular Injury, Walter Reed Army Institute of Research , Silver Spring, MD 20910"},{"name":"Rheumatology Service, Walter Reed Army Medical Center , Washington, D.C. 20307"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasileios C","family":"Kyttaris","sequence":"additional","affiliation":[{"name":"Department of Cellular Injury, Walter Reed Army Institute of Research , Silver Spring, MD 20910"},{"name":"Section of Rheumatology, Washington Hospital Center , Washington, D.C. 20010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhabadeb","family":"Chowdhury","sequence":"additional","affiliation":[{"name":"Department of Cellular Injury, Walter Reed Army Institute of Research , Silver Spring, MD 20910"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violeta","family":"Rus","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Maryland School of Medicine , Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George C","family":"Tsokos","sequence":"additional","affiliation":[{"name":"Department of Cellular Injury, Walter Reed Army Institute of Research , Silver Spring, MD 20910"},{"name":"Department of Medicine, Uniformed Services University of the Health Sciences , Bethesda, MD 20814"},{"name":"Rheumatology Service, Walter Reed Army Medical Center , Washington, D.C. 20307"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2005,9,1]]},"reference":[{"key":"2025032705424854600_R1","first-page":"1448","volume-title":"J. Clin. Invest.","year":"1998"},{"key":"2025032705424854600_R2","first-page":"1908","volume-title":"Arthritis Rheum.","year":"1999"},{"key":"2025032705424854600_R3","first-page":"160","volume-title":"Clin. Exp. Immunol.","year":"2002"},{"key":"2025032705424854600_R4","first-page":"329","volume-title":"J. Exp. Med.","year":"2001"},{"key":"2025032705424854600_R5","first-page":"1114","volume-title":"Arthritis Rheum.","year":"2001"},{"key":"2025032705424854600_R6","first-page":"3325","volume-title":"J. Immunol.","year":"2003"},{"key":"2025032705424854600_R7","first-page":"6048","volume-title":"J. Immunol.","year":"2002"},{"key":"2025032705424854600_R8","first-page":"2496","volume-title":"J. Immunol.","year":"2003"},{"key":"2025032705424854600_R9","first-page":"1879","volume-title":"J. Exp. Med.","year":"1999"},{"key":"2025032705424854600_R10","first-page":"1891","volume-title":"J. Exp. Med.","year":"1999"},{"key":"2025032705424854600_R11","first-page":"395","volume-title":"Nature","year":"2002"},{"key":"2025032705424854600_R12","first-page":"31","volume-title":"Trends Immunol.","year":"2001"},{"key":"2025032705424854600_R13","first-page":"76","volume-title":"Cell Death Differ.","year":"2003"},{"key":"2025032705424854600_R14","first-page":"6785","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1998"},{"key":"2025032705424854600_R15","first-page":"1453","volume-title":"Biochem. Pharmacol.","year":"2003"},{"key":"2025032705424854600_R16","first-page":"1422","volume-title":"Cancer Res.","year":"1999"},{"key":"2025032705424854600_R17","first-page":"176","volume-title":"Scand. J. Immunol.","year":"2001"},{"key":"2025032705424854600_R18","first-page":"74","volume-title":"Clin. Cancer Res.","year":"2001"},{"key":"2025032705424854600_R19","first-page":"675","volume-title":"Nat. Rev. Immunol.","year":"2004"},{"key":"2025032705424854600_R20","first-page":"3685","volume-title":"J. Immunol.","year":"1994"},{"key":"2025032705424854600_R21","first-page":"630","volume-title":"Arthritis Rheum.","year":"1992"},{"key":"2025032705424854600_R22","first-page":"7821","volume-title":"J. Immunol.","year":"2004"},{"key":"2025032705424854600_R23","first-page":"1631","volume-title":"J. Clin. Invest.","year":"2004"},{"key":"2025032705424854600_R24","first-page":"157","volume-title":"Immunity","year":"2002"},{"key":"2025032705424854600_R25","first-page":"1948","volume-title":"Arthritis Rheum.","year":"2003"},{"key":"2025032705424854600_R26","first-page":"115","volume-title":"J. Clin. Invest.","year":"2004"},{"key":"2025032705424854600_R27","first-page":"175","volume-title":"Arthritis Rheum.","year":"2002"},{"key":"2025032705424854600_R28","first-page":"723","volume-title":"Immunity","year":"1998"},{"key":"2025032705424854600_R29","first-page":"787","volume-title":"Immunity","year":"1998"},{"key":"2025032705424854600_R30","first-page":"163","volume-title":"Arthritis Rheum.","year":"2002"},{"key":"2025032705424854600_R31","first-page":"447","volume-title":"J. Cell Biol.","year":"1999"},{"key":"2025032705424854600_R32","first-page":"4216","volume-title":"J. Immunol.","year":"2001"},{"key":"2025032705424854600_R33","first-page":"435","volume-title":"Eur. J. Immunol.","year":"2002"},{"key":"2025032705424854600_R34","first-page":"4189","volume-title":"J. Immunol.","year":"2003"},{"key":"2025032705424854600_R35","first-page":"1795","volume-title":"Science","year":"1992"},{"key":"2025032705424854600_R36","first-page":"2452","volume-title":"J. Immunol.","year":"2001"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/175\/5\/3417\/62621442\/3417.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/175\/5\/3417\/62621442\/3417.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T05:51:02Z","timestamp":1743313862000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/175\/5\/3417\/8036122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,9,1]]},"references-count":36,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2005,9,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.175.5.3417","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2005,9]]},"published":{"date-parts":[[2005,9,1]]}}}