{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T18:45:18Z","timestamp":1789757118257,"version":"4.0.1"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2012,2,1]],"date-time":"2012-02-01T00:00:00Z","timestamp":1328054400000},"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":[[2012,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Altered T cell function in systemic lupus erythematosus (SLE) is determined by various molecular and cellular abnormalities, including increased IL-17 production. Recent evidence suggests a crucial role for signaling lymphocyte activation molecules (SLAMs) in the expression of autoimmunity. In this study, we demonstrate that SLAMF3 and SLAMF6 expression is increased on the surface of SLE T cells compared with normal cells. SLAM coengagement with CD3 under Th17 polarizing conditions results in increased IL-17 production. SLAMF3 and SLAMF6 T cell surface expression and IL-17 levels significantly correlate with disease activity in SLE patients. Both naive and memory CD4+ T cells produce more IL-17 in response to SLAM costimulation as compared with CD28 costimulation. In naive CD4+ cells, IL-17 production after CD28 costimulation peaks on day 3, whereas costimulation with anti-SLAMF3 and anti-SLAMF6 Abs results in a prolonged and yet increasing production during 6 d. Unlike costimulation with anti-CD28, SLAM costimulation requires the presence of the adaptor molecule SLAM-associated protein. Thus, engagement of SLAMF3 and SLAMF6 along with Ag-mediated CD3\/TCR stimulation represents an important source of IL-17 production, and disruption of this interaction with decoy receptors or blocking Abs should mitigate disease expression in SLE and other autoimmune conditions.<\/jats:p>","DOI":"10.4049\/jimmunol.1102773","type":"journal-article","created":{"date-parts":[[2011,12,20]],"date-time":"2011-12-20T04:48:46Z","timestamp":1324356526000},"page":"1206-1212","source":"Crossref","is-referenced-by-count":61,"title":["Increased Expression of SLAM Receptors SLAMF3 and SLAMF6 in Systemic Lupus Erythematosus T Lymphocytes Promotes Th17 Differentiation"],"prefix":"10.1093","volume":"188","author":[{"given":"Madhumouli","family":"Chatterjee","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Rauen","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katalin","family":"Kis-Toth","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasileios C","family":"Kyttaris","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian M","family":"Hedrich","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cox","family":"Terhorst","sequence":"additional","affiliation":[{"name":"Division of Immunology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George C","family":"Tsokos","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,2,1]]},"reference":[{"key":"2025032409482661300_r1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1146\/annurev.immunol.20.091101.091806","article-title":"The B7 family of ligands and its receptors: new pathways for costimulation and inhibition of immune responses","volume":"20","author":"Carreno","year":"2002","journal-title":"Annu. Rev. Immunol."},{"key":"2025032409482661300_r2","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/nri727","article-title":"The B7-CD28 superfamily","volume":"2","author":"Sharpe","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"2025032409482661300_r3","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1146\/annurev.immunol.20.081501.130710","article-title":"Negative regulation of immunoreceptor signaling","volume":"20","author":"Veillette","year":"2002","journal-title":"Annu. Rev. Immunol."},{"key":"2025032409482661300_r4","doi-asserted-by":"crossref","first-page":"5757","DOI":"10.4049\/jimmunol.154.11.5757","article-title":"Naive CD28-deficient T cells can initiate but not sustain an in vitro antigen-specific immune response","volume":"154","author":"Lucas","year":"1995","journal-title":"J. Immunol."},{"key":"2025032409482661300_r5","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1126\/science.7688139","article-title":"Differential T cell costimulatory requirements in CD28-deficient mice","volume":"261","author":"Shahinian","year":"1993","journal-title":"Science"},{"key":"2025032409482661300_r6","doi-asserted-by":"crossref","first-page":"2899","DOI":"10.1182\/blood-2002-02-0445","article-title":"The role of SAP in murine CD150 (SLAM)-mediated T-cell proliferation and interferon \u03b3 production","volume":"100","author":"Howie","year":"2002","journal-title":"Blood"},{"key":"2025032409482661300_r7","doi-asserted-by":"crossref","first-page":"5931","DOI":"10.4049\/jimmunol.174.10.5931","article-title":"Cutting edge: the SLAM family receptor Ly108 controls T cell and neutrophil functions","volume":"174","author":"Howie","year":"2005","journal-title":"J. Immunol."},{"key":"2025032409482661300_r8","doi-asserted-by":"crossref","first-page":"2741","DOI":"10.1002\/1521-4141(200109)31:9<2741::AID-IMMU2741>3.0.CO;2-6","article-title":"Signaling lymphocytic activation molecule (SLAM) regulates T cellular cytotoxicity","volume":"31","author":"Henning","year":"2001","journal-title":"Eur. J. Immunol."},{"key":"2025032409482661300_r9","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.molimm.2007.06.361","article-title":"Enhancement of anti-tumor activity in vitro and in vivo by CD150 and SAP","volume":"45","author":"Mehrle","year":"2008","journal-title":"Mol. Immunol."},{"key":"2025032409482661300_r10","doi-asserted-by":"crossref","first-page":"2821","DOI":"10.1182\/blood-2005-06-2265","article-title":"SLAM\/SLAM interactions inhibit CD40-induced production of inflammatory cytokines in monocyte-derived dendritic cells","volume":"107","author":"R\u00e9thi","year":"2006","journal-title":"Blood"},{"key":"2025032409482661300_r11","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1084\/jem.20031835","article-title":"The cell surface receptor SLAM controls T cell and macrophage functions","volume":"199","author":"Wang","year":"2004","journal-title":"J. Exp. Med."},{"key":"2025032409482661300_r12","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/j.immuni.2007.11.005","article-title":"Consequence of the SLAM-SAP signaling pathway in innate-like and conventional lymphocytes","volume":"27","author":"Veillette","year":"2007","journal-title":"Immunity"},{"key":"2025032409482661300_r13","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/sj.gene.6364453","article-title":"Association of LY9 in UK and Canadian SLE families","volume":"9","author":"Cunninghame Graham","year":"2008","journal-title":"Genes Immun."},{"key":"2025032409482661300_r14","doi-asserted-by":"crossref","first-page":"211","DOI":"10.3109\/08916934.2010.530627","article-title":"SLAMF6-driven co-stimulation of human peripheral T cells is defective in SLE T cells","volume":"44","author":"Chatterjee","year":"2011","journal-title":"Autoimmunity"},{"key":"2025032409482661300_r15","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1056\/NEJMra1100359","article-title":"Systemic lupus erythematosus","volume":"365","author":"Tsokos","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"2025032409482661300_r16","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.coi.2010.10.014","article-title":"The role of SLAM\/CD2 polymorphisms in systemic autoimmunity","volume":"22","author":"Wang","year":"2010","journal-title":"Curr. Opin. Immunol."},{"key":"2025032409482661300_r17","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/S1074-7613(01)00198-4","article-title":"Comparative genomics of the MHC: glimpses into the evolution of the adaptive immune system","volume":"15","author":"Flajnik","year":"2001","journal-title":"Immunity"},{"key":"2025032409482661300_r18","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.immuni.2004.10.009","article-title":"Association of extensive polymorphisms in the SLAM\/CD2 gene cluster with murine lupus","volume":"21","author":"Wandstrat","year":"2004","journal-title":"Immunity"},{"key":"2025032409482661300_r19","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1073\/pnas.98.4.1787","article-title":"The major murine systemic lupus erythematosus susceptibility locus, Sle1, is a cluster of functionally related genes","volume":"98","author":"Morel","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032409482661300_r20","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1126\/science.1125893","article-title":"Regulation of B cell tolerance by the lupus susceptibility gene Ly108","volume":"312","author":"Kumar","year":"2006","journal-title":"Science"},{"key":"2025032409482661300_r21","doi-asserted-by":"crossref","first-page":"18662","DOI":"10.1074\/jbc.M312313200","article-title":"NTB-A, a new activating receptor in T cells that regulates autoimmune disease","volume":"279","author":"Valdez","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2025032409482661300_r22","doi-asserted-by":"crossref","first-page":"291","DOI":"10.4049\/jimmunol.176.1.291","article-title":"Ly9 (CD229)-deficient mice exhibit T cell defects yet do not share several phenotypic characteristics associated with SLAM- and SAP-deficient mice","volume":"176","author":"Graham","year":"2006","journal-title":"J. Immunol."},{"key":"2025032409482661300_r23","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1097\/BOR.0b013e328304b6b5","article-title":"IL-17 and the Th17 lineage in systemic lupus erythematosus","volume":"20","author":"Garrett-Sinha","year":"2008","journal-title":"Curr. Opin. Rheumatol."},{"key":"2025032409482661300_r24","doi-asserted-by":"crossref","first-page":"8761","DOI":"10.4049\/jimmunol.181.12.8761","article-title":"Expanded double negative T cells in patients with systemic lupus erythematosus produce IL-17 and infiltrate the kidneys","volume":"181","author":"Crisp\u00edn","year":"2008","journal-title":"J. Immunol."},{"key":"2025032409482661300_r25","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.clim.2008.01.019","article-title":"Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th17-mediated inflammation in auto-immunity","volume":"127","author":"Wong","year":"2008","journal-title":"Clin. Immunol."},{"key":"2025032409482661300_r26","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1191\/096120300678828703","article-title":"Elevation of proinflammatory cytokine (IL-18, IL-17, IL-12) and Th2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus","volume":"9","author":"Wong","year":"2000","journal-title":"Lupus"},{"key":"2025032409482661300_r27","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/ni1552","article-title":"Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice","volume":"9","author":"Hsu","year":"2008","journal-title":"Nat. Immunol."},{"key":"2025032409482661300_r28","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.4049\/jimmunol.0802948","article-title":"Accelerated pathological and clinical nephritis in systemic lupus erythematosus-prone New Zealand Mixed 2328 mice doubly deficient in TNF receptor 1 and TNF receptor 2 via a Th17-associated pathway","volume":"182","author":"Jacob","year":"2009","journal-title":"J. Immunol."},{"key":"2025032409482661300_r29","doi-asserted-by":"crossref","first-page":"7849","DOI":"10.4049\/jimmunol.178.12.7849","article-title":"Low-dose peptide tolerance therapy of lupus generates plasmacytoid dendritic cells that cause expansion of autoantigen-specific regulatory T cells and contraction of inflammatory Th17 cells","volume":"178","author":"Kang","year":"2007","journal-title":"J. Immunol."},{"key":"2025032409482661300_r30","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1002\/art.1780400928","article-title":"Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus","volume":"40","author":"Hochberg","year":"1997","journal-title":"Arthritis Rheum."},{"key":"2025032409482661300_r31","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1172\/JCI22854","article-title":"Systemic lupus erythematosus serum IgG increases CREM binding to the IL-2 promoter and suppresses IL-2 production through CaMKIV","volume":"115","author":"Juang","year":"2005","journal-title":"J. Clin. Invest."},{"key":"2025032409482661300_r32","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/ni1467","article-title":"Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells","volume":"8","author":"Acosta-Rodriguez","year":"2007","journal-title":"Nat. Immunol."},{"key":"2025032409482661300_r33","doi-asserted-by":"crossref","first-page":"7948","DOI":"10.4049\/jimmunol.180.12.7948","article-title":"Regulation of IL-17 in human CCR6+ effector memory T cells","volume":"180","author":"Liu","year":"2008","journal-title":"J. Immunol."},{"key":"2025032409482661300_r34","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1093\/rheumatology\/35.3.226","article-title":"Active systemic lupus erythematosus is associated with the recruitment of naive\/resting T cells","volume":"35","author":"Gordon","year":"1996","journal-title":"Br. J. Rheumatol."},{"key":"2025032409482661300_r35","first-page":"1922","article-title":"CD45 isoforms expression on CD4+ and CD8+ peripheral blood T-lymphocytes is related to auto-immune processes and hematological manifestations in systemic lupus erythematosus","volume":"126","author":"Neidhart","year":"1996","journal-title":"Schweiz. Med. Wochenschr."},{"key":"2025032409482661300_r36","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1177\/0961203307085246","article-title":"Striking alteration of some populations of T\/B cells in systemic lupus erythematosus: relationship to expression of CD62L or some chemokine receptors","volume":"17","author":"Watanabe","year":"2008","journal-title":"Lupus"},{"key":"2025032409482661300_r37","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1191\/0961203305lu2171oa","article-title":"Increased prevalence of activated CD70+CD4+ T cells in the periphery of patients with systemic lupus erythematosus","volume":"14","author":"Han","year":"2005","journal-title":"Lupus"},{"key":"2025032409482661300_r38","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/90615","article-title":"Regulation of SLAM-mediated signal transduction by SAP, the X-linked lymphoproliferative gene product","volume":"2","author":"Latour","year":"2001","journal-title":"Nat. Immunol."},{"key":"2025032409482661300_r39","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1146\/annurev.immunol.19.1.657","article-title":"X-linked lymphoproliferative disease: a progressive immunodeficiency","volume":"19","author":"Morra","year":"2001","journal-title":"Annu. Rev. Immunol."},{"key":"2025032409482661300_r40","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/90595","article-title":"SAP: natural inhibitor or grand SLAM of T cell activation?","volume":"2","author":"Nichols","year":"2001","journal-title":"Nat. Immunol."},{"key":"2025032409482661300_r41","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/26683","article-title":"The X-linked lymphoproliferative-disease gene product SAP regulates signals induced through the co-receptor SLAM","volume":"395","author":"Sayos","year":"1998","journal-title":"Nature"},{"key":"2025032409482661300_r42","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1590\/S0100-879X2011000400002","article-title":"The role of the SLAM-SAP signaling pathway in the modulation of CD4+ T cell responses","volume":"44","author":"Vilar","year":"2011","journal-title":"Braz. J. Med. Biol. Res."},{"key":"2025032409482661300_r43","doi-asserted-by":"crossref","first-page":"395","DOI":"10.4049\/jimmunol.176.1.395","article-title":"A signal adaptor SLAM-associated protein regulates spontaneous autoimmunity and Fas-dependent lymphoproliferation in MRL-Faslpr lupus mice","volume":"176","author":"Komori","year":"2006","journal-title":"J. Immunol."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/188\/3\/1206\/62479668\/1102773.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/188\/3\/1206\/62479668\/1102773.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T15:22:33Z","timestamp":1743088953000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/188\/3\/1206\/7981229"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,2,1]]},"references-count":43,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2012,2,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1102773","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2012,2]]},"published":{"date-parts":[[2012,2,1]]}}}