Hexokinase 2 is dispensable for T cell-dependent immunity.

Cancer & Metabolism
Manan M MehtaNavdeep Chandel

Abstract

T cells and cancer cells utilize glycolysis for proliferation. The hexokinase (1-4) family of enzymes catalyze the first step of glycolysis. Hexokinase 2 (HK2) is one of the most highly upregulated metabolic enzymes in both cancer and activated T cells. HK2 is required for the development and/or growth of cancer in several cancer models, but the necessity of HK2 in T cells is not fully understood. The clinical applicability of HK2 inhibition in cancer may be significantly limited by any potential negative effects of HK2 inhibition on T cells. Therefore, we investigated the necessity of HK2 for T cell function. In order to identify additional therapeutic cancer targets, we performed RNA-seq to compare in vivo proliferating T cells to T cell leukemia. HK2 was genetically ablated in mouse T cells using a floxed Hk2 allele crossed to CD4-Cre. CD4+ and CD8+ cells from mice were characterized metabolically and tested in vitro. T cell function in vivo was tested in a mouse model of colitis, Th2-mediated lung inflammation, and viral infection. Treg function was tested by crossing Hk2-floxed mice to FoxP3-Cre mice. Hematopoietic function was tested by deleting HK2 from bone marrow with Vav1-iCre. RNA-seq was used to compare T cells prol...Continue Reading

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Sep 13, 2019·Small GTPases·Francisco LlaveroJosé L Zugaza
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Methods Mentioned

BETA
PMA
PCR
flow cytometry
FCS
ELISA
RNA-seq

Software Mentioned

Trimmomatic
TraceFinder
DiffQuik
GSEA
GraphPad
R package edgeR
Xcalibur
count
TopHat
Prism

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