Please use this identifier to cite or link to this item: https://doi.org/10.1038/cdd.2012.144
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. https://doi.org/10.1038/cdd.2012.144
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
URI: http://scholarbank.nus.edu.sg/handle/10635/101832
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.

SCOPUSTM   
Citations

36
checked on Jul 16, 2019

WEB OF SCIENCETM
Citations

36
checked on Jul 16, 2019

Page view(s)

62
checked on Jun 21, 2019

Google ScholarTM

Check

Altmetric


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