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Nat Biotechnol. 2014 Apr;32(4):364-72. doi: 10.1038/nbt.2858. Epub 2014 Mar 16.

Development and function of human innate immune cells in a humanized mouse model.

Author information

1
1] Department of Immunobiology, Yale University, New Haven, Connecticut, USA. [2].
2
1] Baylor Institute for Immunology Research, Dallas, Texas, USA. [2] Biomedical studies program, Baylor University, Waco, Texas, USA.
3
Department of Immunobiology, Yale University, New Haven, Connecticut, USA.
4
1] Department of Laboratory Medicine, Yale University, New Haven, Connecticut, USA. [2] Department of Medicine III, University Hospital Bonn, Bonn, Germany.
5
Division of Hematology, University Hospital Zurich, Zurich, Switzerland.
6
Baylor Institute for Immunology Research, Dallas, Texas, USA.
7
Section of Hematology, Department of Internal Medicine and Yale Comprehensive Cancer Center, Yale University, New Haven, Connecticut, USA.
8
1] Department of Immunobiology, Yale University, New Haven, Connecticut, USA. [2] Howard Hughes Medical Institute, Yale University, New Haven, Connecticut, USA.

Abstract

Mice repopulated with human hematopoietic cells are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, existing humanized mouse models cannot support development of human innate immune cells, including myeloid cells and natural killer (NK) cells. Here we describe two mouse strains called MITRG and MISTRG, in which human versions of four genes encoding cytokines important for innate immune cell development are knocked into their respective mouse loci. The human cytokines support the development and function of monocytes, macrophages and NK cells derived from human fetal liver or adult CD34(+) progenitor cells injected into the mice. Human macrophages infiltrated a human tumor xenograft in MITRG and MISTRG mice in a manner resembling that observed in tumors obtained from human patients. This humanized mouse model may be used to model the human immune system in scenarios of health and pathology, and may enable evaluation of therapeutic candidates in an in vivo setting relevant to human physiology.

Comment in

PMID:
24633240
PMCID:
PMC4017589
DOI:
10.1038/nbt.2858
[Indexed for MEDLINE]
Free PMC Article

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