Leptin promotes glycolytic metabolism to induce dendritic cells activation via STAT3-HK2 pathway.

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-deoxy-d-glucose (2-DG). To explore the signaling pathways involved in leptin-induced HK2 expression, we observed that 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.

• Authors: Ziran Bai, Yunshan Ye, Xiaokang Ye, Bo Yuan, Yawei Tang, Jing Wei, Minli Jin, Guan Wang, Xia Li
• Journal: Immunology letters (Immunol Lett) Vol. 239 Pg. 88-95 (11 2021) ISSN: 1879-0542 [Electronic] Netherlands
• PMID: 34480980 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021. Published by Elsevier B.V.

Chemical References

• Aminosalicylic Acids
• Benzenesulfonates
• LEP protein, human
• Leptin
• NSC 74859
• STAT3 Transcription Factor
• STAT3 protein, human
• HK2 protein, human
• Hexokinase

Topics

• Aminosalicylic Acids (pharmacology)
• Benzenesulfonates (pharmacology)
• Cell Communication (immunology)
• Cell Line
• Cell Proliferation (drug effects)
• Coculture Techniques
• Dendritic Cells (immunology, metabolism)
• Glycolysis (immunology)
• Healthy Volunteers
• Hexokinase (metabolism)
• Humans
• Leptin (metabolism)
• Leukocytes, Mononuclear (immunology, metabolism)
• Primary Cell Culture
• STAT3 Transcription Factor (antagonists & inhibitors, metabolism)
• Signal Transduction (drug effects, immunology)
• Th17 Cells (immunology, metabolism)
• Up-Regulation (immunology)