tetano
Editor, Senior Moderator
Free Radic Biol Med. 2010 Dec 1. [Epub ahead of print]
Elevated mitochondrial superoxide disrupts normal T-cell development to impair adaptive immune responses to an influenza challenge.
Case AJ, McGill JL, Tygrett LT, Shirasawa T, Spitz DR, Waldschmidt TJ, Legge KL, Domann FE.
Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, Iowa 52242, USA.
Abstract
Reactive oxygen species (ROS) are critical in a broad spectrum of cellular processes including signaling, tumor progression, and innate immunity. The essential nature of ROS signaling in the immune systems of Drosophila and zebrafish has been demonstrated; however, the role of ROS, if any, in mammalian adaptive immune system development and function remains unknown. The current work provides the first clear demonstration that thymus specific elevation of mitochondrial superoxide (O(2)(?-)) disrupts normal T-cell development to impair function of the mammalian adaptive immune system. To assess the effect of elevated mitochondrial superoxide in the developing thymus, we used a T-cell specific knockout of manganese superoxide dismutase (i.e. SOD2) and have thus established a murine model to examine the role of mitochondrial superoxide in T-cell development. Conditional loss of SOD2 led to increased superoxide, apoptosis, and developmental defects in the T-cell population resulting in immunodeficiency and susceptibility to influenza A virus (IAV), H1N1. This phenotype was rescued with mitochondrially targeted superoxide scavenging drugs. These new findings demonstrate that loss of regulated levels of mitochondrial superoxide lead to aberrant T-cell development and function, and further suggest that manipulations of mitochondrial superoxide levels may significantly alter clinical outcomes resulting from viral infection.
Copyright ? 2010. Published by Elsevier Inc.
PMID: 21130157 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21130157
Elevated mitochondrial superoxide disrupts normal T-cell development to impair adaptive immune responses to an influenza challenge.
Case AJ, McGill JL, Tygrett LT, Shirasawa T, Spitz DR, Waldschmidt TJ, Legge KL, Domann FE.
Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, Iowa 52242, USA.
Abstract
Reactive oxygen species (ROS) are critical in a broad spectrum of cellular processes including signaling, tumor progression, and innate immunity. The essential nature of ROS signaling in the immune systems of Drosophila and zebrafish has been demonstrated; however, the role of ROS, if any, in mammalian adaptive immune system development and function remains unknown. The current work provides the first clear demonstration that thymus specific elevation of mitochondrial superoxide (O(2)(?-)) disrupts normal T-cell development to impair function of the mammalian adaptive immune system. To assess the effect of elevated mitochondrial superoxide in the developing thymus, we used a T-cell specific knockout of manganese superoxide dismutase (i.e. SOD2) and have thus established a murine model to examine the role of mitochondrial superoxide in T-cell development. Conditional loss of SOD2 led to increased superoxide, apoptosis, and developmental defects in the T-cell population resulting in immunodeficiency and susceptibility to influenza A virus (IAV), H1N1. This phenotype was rescued with mitochondrially targeted superoxide scavenging drugs. These new findings demonstrate that loss of regulated levels of mitochondrial superoxide lead to aberrant T-cell development and function, and further suggest that manipulations of mitochondrial superoxide levels may significantly alter clinical outcomes resulting from viral infection.
Copyright ? 2010. Published by Elsevier Inc.
PMID: 21130157 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21130157