期刊
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
卷 93, 期 2, 页码 -出版社
WILEY
DOI: 10.1111/sji.12981
关键词
glycolysis; macrophage; metabolism; Tim‐ 3
类别
资金
- Beijing Natural Science Foundation [7192145]
- National Nature and Science Fund [81771684, 81971473]
- National Key Research and Development Program of China [AWS16J020, AWS14C014]
Tim-3 controls glycolysis in macrophages, contributing to phenotype shifting; Tim-3 signal blockade increases lactate production without affecting cell proliferation or apoptosis; Tim-3 attenuates glucose uptake in macrophages through inhibiting HK2 expression.
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)-alpha and interleukin (IL)-1 beta 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.
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