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T cell lipid peroxidation induces ferroptosis and prevents immunity to infection.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Matsushita Mai, Freigang Stefan, Schneider Christoph, Conrad Marcus, Bornkamm Georg W, Kopf Manfred,
Project Molecular mechanisms of lipid-induced vascular inflammation in atherosclerosis
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Original article (peer-reviewed)

Journal J Exp Med
Volume (Issue) 212(4)
Page(s) 555 - 568
Title of proceedings J Exp Med
DOI 10.1084/jem.20140857

Open Access

URL http://jem.rupress.org/content/212/4/555.full.pdf+html
Type of Open Access Publisher (Gold Open Access)

Abstract

The selenoenzyme glutathione peroxidase 4 (Gpx4) is a major scavenger of phospholipid hydroperoxides. Although Gpx4 represents a key component of the reactive oxygen species-scavenging network, its relevance in the immune system is yet to be defined. Here, we investigated the importance of Gpx4 for physiological T cell responses by using T cell-specific Gpx4-deficient mice. Our results revealed that, despite normal thymic T cell development, CD8(+) T cells from T(ΔGpx4/ΔGpx4) mice had an intrinsic defect in maintaining homeostatic balance in the periphery. Moreover, both antigen-specific CD8(+) and CD4(+) T cells lacking Gpx4 failed to expand and to protect from acute lymphocytic choriomeningitis virus and Leishmania major parasite infections, which were rescued with diet supplementation of high dosage of vitamin E. Notably, depletion of the Gpx4 gene in the memory phase of viral infection did not affect T cell recall responses upon secondary infection. Ex vivo, Gpx4-deficient T cells rapidly accumulated membrane lipid peroxides and concomitantly underwent cell death driven by ferroptosis but not necroptosis. These studies unveil an essential role of Gpx4 for T cell immunity.
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