OP0315 EFFECTOR CD4 T CELLS REQUIRE SURVIVIN FOR REGULATION OF GLUCOSE METABOLISM AND IFNg PRODUCTION

Background: Interferon-gamma (IFNg) producing effector T cells play the leading role in triggering and perpetuation of inflammation rheumatoid arthritis. Inflammation leads to metabolic reprogramming high energy consumption supporting proliferation IFNg production. Being a part chromosomal passenger complex, oncoprotein survivin is essential for cell proliferation. It has also been identified as marker severe therapy-resistant Thus, we aimed explore association between phenotype CD4 cells. Objectives: We study if mediates glucose dependent mechanism production Methods: were sorted from peripheral blood RA patients healthy controls, activated with aCD3, cultured presence inhibitor YM155 subjected RNA sequencing (Illumina, Life Science). levels supernatants measured by ELISA. To uptake YM155, treated IFNg+aCD3 overnight followed 2NBD-glucose challenge 30 min. Uptake fluorescent probe was flow cytometry. Statistical analysis RNAseq performed R-studio using Bioconductor package DESeq2. Results: Comparison whole-genome transcription profile different BIRC5, coding survivin, demonstrated that BIRC5hi group expressed significantly higher (mRNA, p=10 -26 protein, -4 ). Also, had expression transporter GLUT1 (SLC2A1, p=0.0064) glycolytic enzymes glucose-6-phosphate dehydrogenase (G6PD, -6 ), pyruvate kinase (PFKP, lactate (LDHA, -14 On contrary, key regulator glycolysis 6-phosphofructo-2-kinase (PFKFB3) lower (p=4.4x10 -5 Notably, G6PD PFKFB3 correlated strongly (r=0.880 -0.698, respectively), TBX21 (r=0.811 -0.698) perforin (r=0.781 -0.698). demonstrate functional relevance connection BIRC5 metabolism, inhibited cultures. Survivin inhibition resulted significant increase (p=7x10 ) LDHA (p=0.0089), phosphoglycerate mutase PGAM1 ATF citrate lyase ACLY (p=0.021 p=0.0074, which dignify restoration aerobic glycolysis. Importantly, decreased (p=0.031) reduced (p=0.034). These changes metabolism (p=0.037). Conclusion: The demonstrates strong emerges an important acting through transport. Disclosure Interests: None declared.