ERK Inhibition Promotes Engraftment of Allografts by Reprogramming T‐Cell Metabolism

• DOI: 10.1002/advs.202206768
• Publication Date: 2023-04-04T10:15:32Z
• Authors: Xiaosheng Tan; Changxing Qi; Xiangli Zhao; Lingjuan Sun; Mi Wu; Weiguang Sun; Lianghu Gu; Fengqing Wang; Hao Feng; Xia Huang; Bin Xie; Zhengyi Shi; Peiling Xie; Meng Wu; Yonghui Zhang; Gang Chen
• Keywords: Lycorine; Reprogramming

Abstract Extracellular regulated protein kinases (ERK) signaling is a master regulator of cell behavior, life, and fate. Although ERK pathway shown to be involved in T‐cell activation, little known about its role the development allograft rejection. Here, it reported that activated allograft‐infiltrating T cells. On basis surface plasmon resonance technology, lycorine identified as an ERK‐specific inhibitor. inhibition by significantly prolongs survival stringent mouse cardiac allotransplant model. As compared untreated mice, lycorine‐treated mice show decrease number activation allograft‐infiltrated It further confirmed human cells are less responsive stimulation vitro, indicated their low proliferative rates decreased cytokine production. Mechanistic studies reveal treated with exhibit mitochondrial dysfunction, resulting metabolic reprogramming upon stimulation. Transcriptome analysis reveals enrichment series downregulated terms related immune response, mitogen‐activated kinase cascade, processes. These findings offer new insights into immunosuppressive agents targeting