Bcl-6 directly represses the gene program of the glycolysis pathway

Despite our increasing knowledge of the molecular events that induce the glycolysis pathway in effector T cells, very little is known about the transcriptional mechanisms that dampen the glycolysis program in quiescent cell populations such as memory T cells. Here, we show that the transcription factor Bcl-6 directly repressed genes involved in the glycolysis pathway, including Slc2a1, Slc2a3, Pkm2 and Hk2, in T(H)1 cells exposed to low amounts of interleukin 2 (IL-2). Thus, Bcl-6 plays an opposing role to the IL-2-sensitive glycolytic transcriptional program that c-Myc and HIF-1α promote in effector T cells. Additionally, the Th1-lineage-specifying factor T-bet functionally antagonized the Bcl-6-dependent repression of genes in the glycolysis pathway, implicating the molecular balance between these two factors in metabolic gene program regulation.