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Inhibitors of 3-hyroxy-3-methylgluteryl CoA reductase (statins) can modify the composition of lipid rafts, resulting in alteration of T cell signaling. In this study, we show that atorvastatin targets the distribution of signaling molecules in T cells from SLE patients, by disrupting the colocalization of total Lck and CD45 within lipid rafts, leading to a reduction in the active form of Lck. Upon T cell activation using anti-CD3\/anti-CD28 in vitro, the rapid recruitment of total Lck to the immunological synapse was inhibited by atorvastatin, whereas ERK phosphorylation, which is decreased in SLE T cells, was reconstituted. Furthermore, atorvastatin reduced the production of IL-10 and IL-6 by T cells, implicated in the pathogenesis of SLE. Thus, atorvastatin reversed many of the signaling defects characteristic of SLE T cells. These findings demonstrate the potential for atorvastatin to target lipid raft\u2013associated signaling abnormalities in autoreactive T cells and provide a rationale for its use in therapy of autoimmune disease.<\/jats:p>","DOI":"10.4049\/jimmunol.177.10.7416","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T23:39:04Z","timestamp":1397864344000},"page":"7416-7422","source":"Crossref","is-referenced-by-count":124,"title":["Atorvastatin Restores Lck Expression and Lipid Raft-Associated Signaling in T Cells from Patients with Systemic Lupus Erythematosus"],"prefix":"10.1093","volume":"177","author":[{"given":"Elizabeth C","family":"Jury","sequence":"first","affiliation":[{"name":"Department of Medicine, Centre for Rheumatology, University College London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Isenberg","sequence":"additional","affiliation":[{"name":"Department of Medicine, Centre for Rheumatology, University College London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Mauri","sequence":"additional","affiliation":[{"name":"Department of Medicine, Centre for Rheumatology, University College London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R","family":"Ehrenstein","sequence":"additional","affiliation":[{"name":"Department of Medicine, Centre for Rheumatology, University College London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,11,15]]},"reference":[{"key":"2025032704322571500_R1","first-page":"II18","volume-title":"Circulation","year":"2004"},{"key":"2025032704322571500_R2","first-page":"78","volume-title":"Nature","year":"2002"},{"key":"2025032704322571500_R3","first-page":"1524","volume-title":"J. 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