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T cell immunoglobulin and mucin domain protein 3 inhibits glycolysis in RAW 264.7 macrophages through Hexokinase 2
Scandinavian Journal of Immunology ( IF 3.7 ) Pub Date : 2020-10-08 , DOI: 10.1111/sji.12981
Jiacheng Zhang 1, 2 , Chunmei Hou 2 , Shuaijie Dou 2 , Ge Li 2 , Zhiding Wang 2 , Yiqiong Liu 2 , Yanling Zhang 2 , Renxi Wang 3 , Beifen Shen 2 , Gencheng Han 2
Affiliation  

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.

中文翻译:

T细胞免疫球蛋白和粘蛋白结构域蛋白3通过己糖激酶2抑制RAW 264.7巨噬细胞的糖酵解

T细胞免疫球蛋白和粘蛋白domain-3(Tim-3)是一种免疫检查点分子,在维持先天免疫稳态方面起着至关重要的作用。但是,这些角色的基础机制尚待确定。在这里,我们确定了Tim-3控制巨噬细胞中的糖酵解,从而有助于表型转移。Tim-3信号阻滞显着增加了巨噬细胞的乳酸产量,但不影响细胞增殖或凋亡。Tim-3通过抑制巨噬细胞中的己糖激酶2(HK2)表达来减弱葡萄糖的摄取。Tim-2介导的巨噬细胞糖酵解抑制和促炎细胞因子,肿瘤坏死因子(TNF)-α和白介素(IL)-1β的表达被HK2沉默逆转。最后,我们证明了Tim-3通过STAT1途径抑制HK2表达。
更新日期:2020-10-08
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