Regulating white blood cell activity through the novel universal receptive system.

The understanding of the mechanisms that control key features of immune cells in various disease contexts remains limited, and few techniques are available for manipulating immune cells. Thus, discovering novel strategies for regulating immune cells is essential for gaining insight into their roles in health and disease. In this study, we investigated the potential of the recently described Universal Receptive System to regulate human immune cell functions. This was achieved for the first time by specifically targeting newly discovered surface-bound DNA- and RNA-based receptors on leukocytes using endonucleases and generating "Leukocyte-Tells." Using this approach, 1,496 genes were upregulated, many of which are related to immune cell signaling, migration, endocytosis, and phagocytosis pathways. The antimicrobial and anticancer activities of Leukocyte-Tells exceeded those of control leukocytes in vitro. Under some conditions, such as in antibiofilm experiments against biofilms of Staphylococcus spp., Pseudomonas spp, Candida spp., and other microorganisms, Leukocyte-Tells showed up to 1,000,000-fold higher activities than did control leukocytes. Additionally, Leukocyte-Tells exhibited significantly higher levels of TNF, IL-1β, IFN-γ, IL-6, and IL-10 production. Our findings reveal, for the first time, that the Universal Receptive System can orchestrate fundamental properties of immune cells, including enhanced antimicrobial and anti-tumor activities. This novel approach offers a new avenue for understanding the biology and regulation of white blood cells. Regulation of leucocyte activity is crucial for a properly functioning immune response and developing novel cell-based therapies. Our previous findings demonstrated the existence of nucleic acid-based receptors (Teazeled receptors, TezRs) that govern the responses of various cell types to a diverse array of environmental factors. Here, we discovered that by modulating these TezRs, we could upregulate immune cell signaling, migration, endocytosis, and phagocytosis pathways in leukocytes. By leveraging TezRs, we generated Leukocyte-Tells, which exhibited significantly higher antimicrobial and anticancer activities than the original immune cells.