Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/35245
Title: MITOCHONDRIA LOCALIZED TLR ADAPTOR SARM IS PROAPOPTOTIC DURING T-CELL IMMUNE RESPONSE
Authors: PORKODI PANNEERSELVAM
Keywords: Influenza infection mouse model, proapoptotic SARM, T-cell contraction, neglect- and activation-induced T-cell death, NK/T cell lymphoma
Issue Date: 3-May-2012
Source: PORKODI PANNEERSELVAM (2012-05-03). MITOCHONDRIA LOCALIZED TLR ADAPTOR SARM IS PROAPOPTOTIC DURING T-CELL IMMUNE RESPONSE. ScholarBank@NUS Repository.
Abstract: Following infection clearance, the expanded T cells are terminated to achieve homeostasis, failure of which results in lymphoproliferative and autoimmune diseases. We report that SARM, the most conserved TLR adaptor, is proapoptotic during T-cell contraction. SARM-knockdown T cells survived longer following influenza infection in vivo. During T-cell activation, the SARM level fell before rising, correlating inversely with T-cell proliferation and subsequent clearance. A similar drastic decrease in the level of SARM was observed during in vivo T-cell proliferation. Consistently SARM expression was reduced in NK/T lymphoma patients compared to healthy individuals. SARM-knockdown rescued T cells from both activation- and neglect-induced cell deaths. Mechanistically, SARM expression suppresses Bcl-xL and ERK phosphorylation. The N terminal 27 amino acids, specifically Arginine14 determine the mitochondrial localization of SARM. The mitochondria-localization is crucial for the intrinsic apoptosis mediated by SARM. Collectively, we show how SARM mediates apoptosis, which is crucial for T-cell contraction following infection.
URI: http://scholarbank.nus.edu.sg/handle/10635/35245
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