体内免疫细胞 z-bio 2025-04-30 128

　　Figure Schematic diagram of low immunogenicity delivery of PDL1 mRNA in tol APCs technology for in vivo generation of tolerant antigen presenting cells. (a) The process of delivering PDL1 mRNA to tol APCs in vivo using low immunogenicity lipid nanoparticles (LNPs); (b) The generated tol APCs selectively inhibit activated T cells through the PDL1/PD1 pathway, effectively alleviating symptoms of autoimmune diseases

　　With the support of National Natural Science Foundation of China projects (approval numbers: 52025036, 82173390, 52495014), Professor Wang Yucai's team from the Department of Life Sciences and Medicine at the University of Science and Technology of China has made progress in the study of low immunogenicity lipid nanoparticles (LNPs) delivering mRNA to generate tol APCs in vivo. The related research results, titled "Generation of tolerogenic antigen presenting cells in vivo through the delivery of mRNA encoding PDL1 within lipid nanoparticles," were published online on March 28, 2025 in the journal Nature Biomedical Engineering. The paper link is: https://www.nature.com/articles/s41551-025-01373-0 .

　　In vivo cell engineering technology is considered an important direction for future precision immunotherapy. This technology can achieve functional reprogramming of target cells without the need for in vitro operations, and has the advantages of scalability, standardization, and low cost. Based on this emerging concept, this study developed a low immunogenicity LNP delivery platform that achieves efficient and targeted delivery of PDL1 mRNA by systematically regulating its N/P ratio and group allocation ratio, while significantly reducing the stimulation of the immune system by nanoparticles themselves. This system is capable of efficiently programming antigen-presenting cells in vivo to obtain tol APC phenotype, effectively inducing pathogenic T cell dysfunction and promoting regulatory T cell expansion. In animal models of autoimmune diseases such as rheumatoid arthritis and ulcerative colitis, the tol APCs generated by this strategy exhibit significant therapeutic effects, accurately regulating immune balance and inhibiting disease progression. This strategy breaks through the problems of complex operation, high cost, and difficulty in popularizing individual customization in traditional in vitro induction of tol APCs methods, significantly improving the clinical feasibility of the technology.

　　Compared with conventional mRNA delivery systems widely used in vaccines, the low immunogenicity LNP system developed in this study achieves a balance between delivery efficiency and immune tolerance. Its characteristic is to maintain efficient mRNA expression while avoiding APCs activation into immune mature phenotype (such as upregulation of co stimulatory molecules such as CD80/CD86/CD40), which is the key to achieving in vivo induction of tol APCs. This study not only provides a new strategy for the treatment of autoimmune diseases, but also provides technical support for the cutting-edge direction of "in vivo immune cell engineering", with broad clinical translation prospects.