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

• Published in: Immunology letters Vol. 239; pp. 88 - 95
• Main Authors: Bai, Ziran, Ye, Yunshan, Ye, Xiaokang, Yuan, Bo, Tang, Yawei, Wei, Jing, Jin, Minli, Wang, Guan, Li, Xia
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2021
• Subjects: Aminosalicylic Acids - pharmacology; Benzenesulfonates - pharmacology; Cell Communication - immunology; Cell Line; Cell Proliferation - drug effects; Coculture Techniques; Dendritic cell; Dendritic Cells - immunology; Dendritic Cells - metabolism; Glycolysis; Glycolysis - immunology; Healthy Volunteers; Hexokinase - metabolism; HK2; Humans; Leptin; Leptin - metabolism; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Primary Cell Culture; Signal Transduction - drug effects; Signal Transduction - immunology; STAT3 Transcription Factor - antagonists & inhibitors; STAT3 Transcription Factor - metabolism; Th17 cell; Th17 Cells - immunology; Th17 Cells - metabolism; Up-Regulation - immunology; Glycolysis; Dendritic cell; Th17 cell; Leptin; HK2
• ISSN: 0165-2478; 1879-0542
• DOI: 10.1016/j.imlet.2021.08.006

•Leptin-activated DCs promote the proliferation of PBMC and up-regulates the percentage of Th17 cells.•DCs activation by leptin depends on glycolysis.•Leptin enhances HK2 expression on DCs via STAT3 pathway. 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. [Display omitted]