Please use this identifier to cite or link to this item: https://doi.org/10.1038/cdd.2012.144
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dc.titleT-cell death following immune activation is mediated by mitochondria-localized SARM
dc.contributor.authorPanneerselvam, P.
dc.contributor.authorSingh, L.P.
dc.contributor.authorSelvarajan, V.
dc.contributor.authorChng, W.J.
dc.contributor.authorNg, S.B.
dc.contributor.authorTan, N.S.
dc.contributor.authorHo, B.
dc.contributor.authorChen, J.
dc.contributor.authorDing, J.L.
dc.date.accessioned2014-10-27T08:41:29Z
dc.date.available2014-10-27T08:41:29Z
dc.date.issued2013
dc.identifier.citationPanneerselvam, P., Singh, L.P., Selvarajan, V., Chng, W.J., Ng, S.B., Tan, N.S., Ho, B., Chen, J., Ding, J.L. (2013). T-cell death following immune activation is mediated by mitochondria-localized SARM. Cell Death and Differentiation 20 (3) : 478-489. ScholarBank@NUS Repository. https://doi.org/10.1038/cdd.2012.144
dc.identifier.issn13509047
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/101832
dc.description.abstractFollowing acute-phase infection, activated T cells are terminated to achieve immune homeostasis, failure of which results in lymphoproliferative and autoimmune diseases. We report that sterile - and heat armadillo-motif- containing protein (SARM), the most conserved Toll-like receptors adaptor, is proapoptotic during T-cell immune response. SARM expression is significantly reduced in natural killer (NK)/T lymphoma patients compared with healthy individuals, suggesting that decreased SARM supports NK/T-cell proliferation. T cells knocked down of SARM survived and proliferated more significantly compared with wild-type T cells following influenza infection in vivo. During activation of cytotoxic T cells, the SARM level fell before rising, correlating inversely with cell proliferation and subsequent T-cell clearance. SARM knockdown rescued T cells from both activation- and neglect-induced cell deaths. The mitochondria-localized SARM triggers intrinsic apoptosis by generating reactive oxygen species and depolarizing the mitochondrial potential. The proapoptotic function is attributable to the C-terminal sterile alpha motif and Toll/interleukin-1 receptor domains. Mechanistically, SARM mediates intrinsic apoptosis via B cell lymphoma-2 (Bcl-2) family members. SARM suppresses B cell lymphoma-extra large (Bcl-xL) and downregulates extracellular signal-regulated kinase phosphorylation, which are cell survival effectors. Overexpression of Bcl-xL and double knockout of Bcl-2 associated X protein and Bcl-2 homologous antagonist killer substantially reduced SARM-induced apoptosis. Collectively, we have shown how T-cell death following infection is mediated by SARM-induced intrinsic apoptosis, which is crucial for T-cell homeostasis. © 2013 Macmillan Publishers Limited All rights reserved.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1038/cdd.2012.144
dc.sourceScopus
dc.subjectadoptive transfer mouse model
dc.subjectinfluenza infection
dc.subjectintrinsic T-cell death by SARM
dc.subjectneglect- and activation-induced cell death
dc.subjectNK/T-cell lymphoma
dc.typeArticle
dc.contributor.departmentBIOLOGICAL SCIENCES
dc.description.doi10.1038/cdd.2012.144
dc.description.sourcetitleCell Death and Differentiation
dc.description.volume20
dc.description.issue3
dc.description.page478-489
dc.description.codenCDDIE
dc.identifier.isiut000317264100010
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