Please use this identifier to cite or link to this item:
Title: T-cell death following immune activation is mediated by mitochondria-localized SARM
Authors: Panneerselvam, P.
Singh, L.P.
Selvarajan, V.
Chng, W.J.
Ng, S.B.
Tan, N.S.
Ho, B.
Chen, J.
Ding, J.L. 
Keywords: adoptive transfer mouse model
influenza infection
intrinsic T-cell death by SARM
neglect- and activation-induced cell death
NK/T-cell lymphoma
Issue Date: 2013
Citation: Panneerselvam, 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.
Abstract: Following 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.
Source Title: Cell Death and Differentiation
ISSN: 13509047
DOI: 10.1038/cdd.2012.144
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.