Title | Development and function of human innate immune cells in a humanized mouse model. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Rongvaux A, Willinger T, Martinek J, Strowig T, Gearty SV, Teichmann LL, Saito Y, Marches F, Halene S, A Palucka K, Manz MG, Flavell RA |
Journal | Nat Biotechnol |
Volume | 32 |
Issue | 4 |
Pagination | 364-72 |
Date Published | 2014 Apr |
ISSN | 1546-1696 |
Keywords | Animals, Humans, Immunity, Innate, Killer Cells, Natural, Leukemic Infiltration, Mice, Mice, Transgenic, Myeloid Cells, Neoplasms, Experimental, Transplantation, Heterologous |
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. |
DOI | 10.1038/nbt.2858 |
Alternate Journal | Nat. Biotechnol. |
PubMed ID | 24633240 |
PubMed Central ID | PMC4017589 |
Grant List | R01 CA140602 / CA / NCI NIH HHS / United States CA140602 / CA / NCI NIH HHS / United States P01 CA084512 / CA / NCI NIH HHS / United States R01 CA129350 / CA / NCI NIH HHS / United States / / Howard Hughes Medical Institute / United States CA84512 / CA / NCI NIH HHS / United States R01 CA156689 / CA / NCI NIH HHS / United States CA129350 / CA / NCI NIH HHS / United States CA156689 / CA / NCI NIH HHS / United States |
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