T细胞功能稳定性 z-bo 2020-09-15 528

　　Recently, the Shanghai Pasteur Institute's Molecular Immunology Research Group of the Chinese Academy of Sciences published a paper titled "PIM1 kinase phosphorylates human transcription factor FOXP3 on Serine 422 to regulate inflammation" ("Journal of Biological Chemistry" published online. The The research was conducted under inflammatory conditions.) A new mechanism that negatively regulates the functional stability of Treg has been discovered, which can be used to treat immune-related diseases (infectious diseases, autoimmune diseases, allergic diseases, tumors, etc.), organ transplants, etc. Provide drug targeting and clinical intervention. FOXP3 is the main transcription factor that determines the development, differentiation and function of regulated T cells (Treg), and is an important function of Treg cell immunosuppressive activity. Although phosphorylation modification has a broad and important effect on the regulation of protein activity, the molecular mechanism that regulates the phosphorylation of FOXP3 protein activity is still poorly understood.

　　Shanghai Pasteur Institute of Molecular Immunology doctoral student Li Zhiyuan and other researchers under the guidance of Li Bin, PIM1 kinase cooperated with Zhang Yu's group of Shanghai Jiaotong University to phosphorylate the FOXP3 protein at the Ser422 site. It has been found that it can be specifically catalyzed. This site-specific phosphorylation weakens the ability of FOXP3 to bind to chromatin, thereby weakening its transcriptional regulatory activity. The researchers also found that the inflammatory factor IL-6 rapidly induced Treg cells to express PIM1 protein, while TCR-activated Treg cells significantly reduced PIM1 expression. Using shRNA to down-regulate PIM1 expression or treating TIM cells with PIM1 inhibitors, both can significantly increase the immunosuppressive activity of Treg cells. This research is essential to reduce PIM1 kinase activity by targeting and improving the immunosuppressive activity of TIM cells in vivo or in vitro and leading to the clinical application of Treg cells.

　　The research is a general project of the School of Life Sciences of the National Natural Science Foundation of China, the first Sino-US (NFSC-NIH) biomedical cooperation pilot project and a major project of the School of Medicine, the 100 Talents Program of the Chinese Academy of Sciences, and the Shanghai Science and Technology Commission Funded by the Youth Science and Technology Gold Star Program.