Human NK cell development in hIL-7 and hIL-15 knockin NOD/SCID/IL2rgKO mice

Life Sci Alliance. 2019 Apr 1;2(2):e201800195. doi: 10.26508/lsa.201800195. Print 2019 Apr.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD56 Antigen / metabolism
  • Cell Differentiation*
  • Female
  • Fetal Blood / cytology
  • Gene Knock-In Techniques*
  • Humans
  • Interleukin-15 / blood*
  • Interleukin-15 / genetics*
  • Interleukin-7 / blood*
  • Interleukin-7 / genetics*
  • Killer Cells, Natural / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Mice, SCID
  • Mice, Transgenic
  • Models, Animal
  • Thymus Gland / cytology
  • Transcriptome
  • Transplantation, Heterologous

Substances

  • CD56 Antigen
  • IL15 protein, human
  • IL7 protein, human
  • Interleukin-15
  • Interleukin-7
  • NCAM1 protein, human