Abstract
The immune system encompasses acquired and innate immunity that matures through interaction with microenvironmental components. Cytokines serve as environmental factors that foster functional maturation of immune cells. Although NOD/SCID/IL2rgKO (NSG) humanized mice support investigation of human immunity in vivo, a species barrier between human immune cells and the mouse microenvironment limits human acquired as well as innate immune function. To study the roles of human cytokines in human acquired and innate immune cell development, we created NSG mice expressing hIL-7 and hIL-15. Although hIL-7 alone was not sufficient for supporting human NK cell development in vivo, increased frequencies of human NK cells were confirmed in multiple organs of hIL-7 and hIL-15 double knockin (hIL-7xhIL-15 KI) NSG mice engrafted with human hematopoietic stem cells. hIL-7xhIL-15 KI NSG humanized mice provide a valuable in vivo model to investigate development and function of human NK cells.
Highlights
Cytokine receptor signaling is indispensable for reconstitution of the human immune system following hematopoietic stem cell (HSC) therapy
A recent report demonstrated a role of IL-15 in anticancer immunity in that the frequencies of breast cancer metastasis were more frequent in IL-15 knockout (IL-15KO) mice than those in IL-15 transgenic mice or in C57BL/6 control mice (Gillgrass et al, 2014)
We developed NOD/SCID/IL2rgKO (NSG) mice to investigate the in vivo dynamics of the human immune system (Ishikawa et al, 2005; Shultz et al, 2005)
Summary
Cytokine receptor signaling is indispensable for reconstitution of the human immune system following hematopoietic stem cell (HSC) therapy. IL-7 promotes differentiation and maturation of T cells, B cells (Mackall et al, 2011), and innate lymphoid cells (Moro et al, 2010). In addition to the development of mature lymphoid cells, IL-7 signaling plays a pivotal role at the level of progenitor cells. Studies of IL-7– or IL-7R–deficient mice revealed multiple defects in T- and B-cell development (Peschon et al, 1994; von Freeden-Jeffry et al, 1995). Studies using IL-15 transgenic mice (Fehniger et al, 2001) and IL-15 knockout (IL-15KO) mice (Kennedy et al, 2000) have shown IL-15 to be essential in the development of NK cells, natural killer T (NKT) cells, and memory CD8+ T cells. A recent report demonstrated a role of IL-15 in anticancer immunity in that the frequencies of breast cancer metastasis were more frequent in IL-15KO mice than those in IL-15 transgenic mice or in C57BL/6 control mice (Gillgrass et al, 2014)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
