Survivin promotes a glycolytic switch in CD4 T cells by suppressing the transcription of PFKFB3 in rheumatoid arthritis.

In this study, we explore the role of nuclear survivin in maintaining the effector phenotype of IFNγ-producing T cells acting through the transcriptional control of glucose utilization. High expression of survivin in CD4T cells was associated with IFNγ-dependent phenotype and anaerobic glycolysis. Transcriptome of CD4 cells and sequencing of survivin-bound chromatin showed that nuclear survivin had a genome-wide and motif-specific binding to regulatory regions of the genes controlling cell metabolism. Survivin coprecipitates with transcription factors IRF1 and SMAD3, which repressed the transcription of the metabolic check-point enzyme phosphofructokinase 2 gene and promoted anaerobic glycolysis. Combining transcriptome analyses of CD4 cells and functional studies in glucose metabolism, we demonstrated that the inhibition of survivin reverted production, inhibited glucose uptake, and reduces interferon effects in CD4 cells. These results present a survivin-dependent mechanism in coordinating the metabolic adaptation of CD4T cells and propose an attractive strategy to counteract IFNγ-dependent inflammation in autoimmunity.