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

• Published in: mBio 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
• Language: English
• 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

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...