Regulating Human T Lymphocytes Through Magnetogenetic Tools

The field of synthetic biology has expanded the possibilities for controlling cellular functions, particularly in the development of mammalian cells for therapeutic applications. This study explored the application of magnetogenetic tools to regulate T cell activity, a crucial aspect of developing advanced immunotherapies. Magnetogenetic tools use magnetic fields to remotely control engineered ion channels and protein domains, providing non-invasive, deep-tissue stimulation that overcomes the limitations of traditional methods. We investigated the effects of three magnetogenetic tools - engineered TRPV1 (TRP1-Fer) and TRPV4 (TRP4-Fer) channels, and Electromagnetic Perceptive Gene (EPG) - in Jurkat cells. First, calcium concentration measurements confirmed the activity of these tools within the cells. Using qPCR and proteomics analysis, we then analyzed their impact on T cell activation, calcium signaling, mitochondrial function, membrane integrity, and gene expression under both stimulated (with antigens) and non-stimulated conditions. Our results revealed significant upregulation of activation and calcium-handling proteins in stimulated cells, indicating enhanced activation and cytoskeletal dynamics compared to controls. However, in non-stimulated cells, the magnetogenetic tools unexpectedly led to deactivation of T cells. This investigation showed that while magnetic induction alone deactivated the cells, antigen stimulation in conjunction with magnetic induction amplified cell activation. This study highlights the potential of magnetogenetics to precisely modulate T cell functions, presenting promising avenues for more effective and controlled immunotherapies. However, the findings also underscore the need for careful optimization to mitigate potential adverse effects on cellular integrity and function.