The inhibitory receptor LAG3 affects NK cell IFN-γ production through glycolysis and the PSAT1/STAT1/IFNG pathway

We demonstrate that lymphocyte activation gene 3 (LAG3) expression is upregulated on natural killer (NK) cells during HIV infection. LAG3 inhibits glycolysis in NK cells and also upregulates PSAT1 expression to suppress activation of the STAT1/IFNG pathway, thus restricting interferon-gamma producti...

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Published inmBio Vol. 16; no. 6; p. e0023025
Main Authors Ge, Hongchi, Guo, Nan, Liu, Yufei, Lang, Bin, Yin, Xiaowan, Yu, Xiaowen, Zhang, Zining, Fu, Yajing, Ding, Haibo, Hu, Qinghai, Han, Xiaoxu, Geng, Wenqing, Shang, Hong, Jiang, Yongjun
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 11.06.2025
Subjects
Antigens, CD - genetics
Antigens, CD - immunology
Antigens, CD - metabolism
Female
Glycolysis
HIV
HIV Infections - immunology
Humans
IFN-γ
Immunology
Interferon-gamma - metabolism
Killer Cells, Natural - immunology
Killer Cells, Natural - metabolism
LAG3
Lymphocyte Activation Gene 3 Protein
Male
Research Article
Signal Transduction
STAT1
STAT1 Transcription Factor - genetics
STAT1 Transcription Factor - metabolism
IFN-γ
LAG3
HIV
STAT1
NK
glycolysis
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Summary:We demonstrate that lymphocyte activation gene 3 (LAG3) expression is upregulated on natural killer (NK) cells during HIV infection. LAG3 inhibits glycolysis in NK cells and also upregulates PSAT1 expression to suppress activation of the STAT1/IFNG pathway, thus restricting interferon-gamma production by NK cells. These results provide new clues to study the effects of LAG3 on the metabolism and functional exhaustion of NK cells and offer a potential target for the treatment of HIV.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
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The authors declare no conflict of interest.
Hongchi Ge, Nan Guo, Yufei Liu, and Bin Lang contributed equally to this article. The author order was determined by drawing straws.
ISSN:2150-7511
2150-7511
DOI:10.1128/mbio.00230-25