Journal
IMMUNOLOGY AND CELL BIOLOGY
Volume 100, Issue 8, Pages 624-635Publisher
WILEY
DOI: 10.1111/imcb.12564
Keywords
human cytokine; humanized mice; innate immunity; transposon
Categories
Funding
- National Natural Science Foundation of China [81901643, 81870091]
- opening object of Key Laboratory of Organ Regeneration and Transplantation (Jilin University), Ministry of Education [2020JC04]
- General Fund of China Postdoctoral Science Foundation [64, 2018M641786]
- Youth Fund of the First Hospital of Jilin University [00400050094]
- Science Development Project of Jilin Province [20190201295JC, 20200703012ZP]
- COVID-19 of Jilin Province [20200901006SF]
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Researchers have successfully achieved long-term production of human cytokines in immunodeficient mice using a transposon-plasmid-based hydrodynamic injection approach. This method can promote the reconstitution of human immune function in mice.
Humanized mice reconstituted with a functional human immune system (HIS) are instrumental in studying human immunity and immune disorders in vivo. The poor or lack of cross-reactivity between mouse cytokines and human cells limits the development and/or function of human immune cell subsets including human myeloid, natural killer and B cells. Here we explored the potential to achieve long-term production of human cytokines in immunodeficient mice using a transposon-plasmid-based hydrodynamic injection approach. We constructed a transposon-plasmid carrying five human cytokine coding sequences (named PB-5F), and observed that four of the cytokines (granulocyte-macrophage colony-stimulating factor, interleukin (IL)-15, IL-6 and IL-3) were detectable in sera and three (granulocyte-macrophage colony-stimulating factor, IL-15 and IL-6) showed long-term production in immunodeficient mice that received a single hydrodynamic injection of PB-5F plus the transposase plasmid (Super PB). Furthermore, a single injection of PB-5F/Super PB markedly enhanced the reconstitution of human myeloid cells and natural killer cells, and promoted human B-cell maturation in HIS mice. Taken together, our data revealed that hydrodynamic injection of the PB-5F/Super PB vectors may serve as a convenient and efficacious means to promote human immune function in HIS mice.
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