Hexokinase 2 is dispensable for T cell-dependent immunity

• DOI: 10.1186/s40170-018-0184-5
• Publication Date: 2018-08-17T07:32:29Z
• Authors: Manan M. Mehta; Samuel E. Weinberg; Elizabeth M. Stei...; Krishan Chhiba; Carlos Alberto Ma...; Peng Gao; Harris R. Perlman; Paul Bryce; Nissim Hay; Navdeep S. Chandel
• Keywords: Hexokinase

T cells and cancer utilize glycolysis for proliferation. The hexokinase (1-4) family of enzymes catalyze the first step glycolysis. Hexokinase 2 (HK2) is one most highly upregulated metabolic in both activated cells. HK2 required development and/or growth several models, but necessity not fully understood. clinical applicability inhibition may be significantly limited by any potential negative effects on Therefore, we investigated cell function. In order to identify additional therapeutic targets, performed RNA-seq compare vivo proliferating leukemia.HK2 was genetically ablated mouse using a floxed Hk2 allele crossed CD4-Cre. CD4+ CD8+ from mice were characterized metabolically tested vitro. function model colitis, Th2-mediated lung inflammation, viral infection. Treg crossing Hk2-floxed FoxP3-Cre mice. Hematopoietic deleting bone marrow with Vav1-iCre. used response virus primary T-ALL leukemia induced mutant Notch1 expression.We unexpectedly report that largely dispensable vitro activation, proliferation, differentiation. Loss does impair immunity causes only small impairment pathological inflammation. or hematopoiesis vivo. One hundred sixty-seven genes identified as being differentially expressed between enzyme requirement various models has been described previously. Our finding are able withstand loss indicates promising candidate therapy. Furthermore, other targets could spare