PT  - JOURNAL ARTICLE
AU  - Malin C. Erlandsson
AU  - Karin M.E. Andersson
AU  - Nina Y. Oparina
AU  - Venkataragavan Chandrasekaran
AU  - Anastasios Damdimopoulos
AU  - Maria-Jose Garcia-Bonete
AU  - Zakaria Einbeigi
AU  - Sofia T. Silfverswärd
AU  - Marcela Pekna
AU  - Gergely Katona
AU  - Maria I. Bokarewa
TI  - Chromatin binding of survivin regulates glucose metabolism in the IFN-γ producing CD4<sup>+</sup> T cells
AID  - 10.1101/2021.10.05.463166
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.10.05.463166
4099  - http://biorxiv.org/content/early/2021/10/05/2021.10.05.463166.short
4100  - http://biorxiv.org/content/early/2021/10/05/2021.10.05.463166.full
AB  - Interferon-gamma (IFNγ) producing T cells develop metabolic adaptation required for their effector functions in tumour biology, autoimmunity and antiviral defence.Using sorted CD4+ cells we demonstrated that glycolytic switch and high glucose uptake in IFNγ-producing cells was associated with survivin expression. Inhibition of survivin restored glycolysis by upregulating the transcription of phosphofructokinase PFKFB3 and reducing glucose uptake. Integration of the whole-genome sequencing of the chromatin immunoprecipitated with survivin with transcription changes in CD4+ cells after survivin inhibition revealed co-localization of survivin, IRF1 and SMAD3 in the regulatory elements paired to the differentially expressed genes. Western blot demonstrated direct binding of survivin to IRF1 and SMAD3. Functionally, inhibition of survivin repressed IFNγ signalling and activated SMAD3-dependent protein remodelling, which resulted in the effector-to-memory transition of CD4+ cells. These findings demonstrate the key role of survivin in IFNγ-dependent metabolic adaptation and identify survivin inhibition as an attractive strategy to counteract these effects.Competing Interest StatementThe authors have declared no competing interest.