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

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.

journal_name

Nat Biotechnol

journal_title

Nature biotechnology

authors

Rongvaux A,Willinger T,Martinek J,Strowig T,Gearty SV,Teichmann LL,Saito Y,Marches F,Halene S,Palucka AK,Manz MG,Flavell RA

doi

10.1038/nbt.2858

subject

Has Abstract

pub_date

2014-04-01 00:00:00

pages

364-72

issue

4

eissn

1087-0156

issn

1546-1696

pii

nbt.2858

journal_volume

32

pub_type

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