T cell immunoglobulin and mucin domain protein 3 inhibits glycolysis in RAW 264.7 macrophages through Hexokinase 2. (24th October 2020)

• Record Type: Journal Article
• Authors: Zhang, Jiacheng; Hou, Chunmei; Dou, Shuaijie; Li, Ge; Wang, Zhiding; Liu, Yiqiong; Zhang, Yanling; Wang, Renxi; Shen, Beifen; Han, Gencheng
• Is Part Of: Scandinavian journal of immunology. Volume 93:Number 2(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-10-24
• Subjects: glycolysis -- macrophage -- metabolism -- Tim‐3; Immunology -- Periodicals; 571.96
• DOI: 10.1111/sji.12981
• Languages: English
• ISSNs: 0300-9475

Abstract

Abstract: T cell immunoglobulin and mucin domain‐3 (Tim‐3), an immune checkpoint molecule, plays critical roles in maintaining innate immune homeostasis; however, the mechanisms underlying these roles remain to be determined. Here, we determined that Tim‐3 controls glycolysis in macrophages and thus contributes to phenotype shifting. Tim‐3 signal blockade significantly increases lactate production by macrophages, but does not influence cell proliferation or apoptosis. Tim‐3 attenuates glucose uptake by inhibiting hexokinase 2 (HK2) expression in macrophages. Tim‐3‐mediated inhibition of macrophage glycolysis and the expression of proinflammatory cytokines, tumour necrosis factor (TNF)‐α and interleukin (IL)‐1β are reversed by HK2 silencing. Finally, we demonstrated that Tim‐3 inhibits HK2 expression via the STAT1 pathway. We have thus discovered a new way by which Tim‐3 modulates macrophage function.