RETRACTED: The protein LEM promotes CD8+ T cell immunity through effects on mitochondrial respiration (Retracted Article)

被引:39
作者
Okoye, Isobel [1 ]
Wang, Lihui [1 ]
Pallmer, Katharina [2 ]
Richter, Kirsten [2 ]
Ichimura, Takahuru [3 ]
Haas, Robert [4 ]
Crouse, Josh [2 ]
Choi, Onjee [1 ]
Heathcote, Dean [1 ]
Lovo, Elena [1 ]
Mauro, Claudio [4 ]
Abdi, Reza [3 ]
Oxenius, Annette [2 ]
Rutschmann, Sophie [1 ]
Ashton-Rickardt, Philip G. [1 ,3 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Med, Sect Immunobiol,Div Inflammat & Immunol, London SW7 2AZ, England
[2] ETHZ, Inst Microbiol, CH-8093 Zurich, Switzerland
[3] Harvard Univ, Sch Med, Brigham & Womens Hosp, Transplantat Res Ctr, Boston, MA 02215 USA
[4] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England
基金
瑞士国家科学基金会; 英国惠康基金; 英国医学研究理事会;
关键词
CHRONIC VIRAL-INFECTION; MESSENGER-RNA DECAY; VIRUS-INFECTION; MEMORY; ANTIGEN; DIFFERENTIATION; CANCER; MICE; LYMPHOCYTES; EXHAUSTION;
D O I
10.1126/science.aaa7516
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Protective CD8(+) T cell-mediated immunity requires a massive expansion in cell number and the development of long-lived memory cells. Using forward genetics in mice, we identified an orphan protein named lymphocyte expansion molecule (LEM) that promoted antigen-dependent CD8(+) T cell proliferation, effector function, and memory cell generation in response to infection with lymphocytic choriomeningitis virus. Generation of LEM-deficient mice confirmed these results. Through interaction with CR6 interacting factor (CRIF1), LEM controlled the levels of oxidative phosphorylation (OXPHOS) complexes and respiration, resulting in the production of pro-proliferative mitochondrial reactive oxygen species (mROS). LEM provides a link between immune activation and the expansion of protective CD8(+) T cells driven by OXPHOS and represents a pathway for the restoration of long-term protective immunity based on metabolically modified cytotoxic CD8(+) T cells.
引用
收藏
页码:995 / 1001
页数:7
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