T cell lipid peroxidation induces ferroptosis and prevents immunity to infection

Matsushita, Mai; Freigang, Stefan Bernd; Schneider, Christoph; Conrad, Marcus; Bornkamm, Georg W; Kopf, Manfred (2015). T cell lipid peroxidation induces ferroptosis and prevents immunity to infection. The Journal of experimental medicine, 212(4), pp. 555-568. Rockefeller Univ. Press 10.1084/jem.20140857

[img]
Preview
Text
J Exp Med-2015-Matsushita-555-68.pdf - Published Version
Available under License Creative Commons: Attribution-Noncommercial-Share Alike (CC-BY-NC-SA).
After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

Download (4MB) | Preview

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology

UniBE Contributor:

Freigang, Stefan Bernd

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1540-9538

Publisher:

Rockefeller Univ. Press

Language:

English

Submitter:

Doris Haefelin

Date Deposited:

13 Jul 2015 14:23

Last Modified:

30 Mar 2016 11:15

Publisher DOI:

10.1084/jem.20140857

PubMed ID:

25824823

BORIS DOI:

10.7892/boris.70218

URI:

https://boris.unibe.ch/id/eprint/70218

Actions (login required)

Edit item Edit item
Provide Feedback