T cell immunoglobulin and mucin domain protein 3 inhibits glycolysis in RAW 264.7 macrophages through Hexokinase 2.

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.

journal_name

Scand J Immunol

authors

Zhang J,Hou C,Dou S,Li G,Wang Z,Liu Y,Zhang Y,Wang R,Shen B,Han G

doi

10.1111/sji.12981

subject

Has Abstract

pub_date

2021-02-01 00:00:00

pages

e12981

issue

2

eissn

0300-9475

issn

1365-3083

journal_volume

93

pub_type

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