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Leptin promoted glycolytic metabolism to induce DCs activation via STAT3-HK2 pathway
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  • Yunshan Ye,
  • Ziran Bai,
  • Xiaokang Ye,
  • Bo Yuan,
  • Yawei Tang,
  • Wei Jing,
  • Minli Jin,
  • Guan Wang,
  • xia li
Yunshan Ye
Dalian Medical University
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Ziran Bai
Dalian Medical University
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Xiaokang Ye
Dalian Medical University
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Bo Yuan
Dalian Medical University
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Yawei Tang
Dalian Medical University
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Wei Jing
Dalian Medical University
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Minli Jin
Dalian Medical University
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Guan Wang
Dalian Medical University
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xia li
Dalian Medical University
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Abstract

Leptin is over-secreted in many autoimmune diseases, which can promote dendritic cells (DCs) maturation and up-regulate the expression of inflammatory cytokines, but the underlying mechanisms are not fully elucidated. Considering the major role of leptin in maintaining energy balance and the significant role of glycolysis in DCs activation, our study aims to investigate whether leptin promotes the activation of DCs via glycolysis and its underlying mechanisms. We demonstrated that leptin promoted the activation of DCs, including up-regulating the expression of co-stimulatory molecules and inflammatory cytokines, enhancing the proliferation and T helper 17 (Th17) cell ratio in peripheral blood mononuclear cells (PBMC) co-cultured with leptin-stimulated DCs. Leptin also enhanced DCs glycolysis with increased glucose consumption, lactate production, and the expression of hexokinase 2 (HK2). In addition, the activation of DCs stimulated by leptin could be inhibited by the glycolysis inhibitor 2-DG. To explore the signaling pathways involved in leptin-induced HK2 expression, we observed that only the inhibitors of STAT3 (NSC74859) could repress the enhancement of HK2 triggered by leptin stimulation. Therefore, our results indicated that leptin promoted glycolytic metabolism to induce DCs activation via STAT3-HK2 pathway.