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Title:
Development and function of human innate immune cells in a humanized mouse model | Nature Biotechnology
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A mouse bearing multiple human cytokine genes enables in vivo development and function of various human innate immune cell types. 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.
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nature portfolio permissions reprints privacy policy humanized neonatal nod/scid/il2rgamma advertising human-hemato-lymphoid-system mice nature nod/scid mice engineered social media human il-3/gm-csf knock specific tumor-reactive ctl membrane-bound human scf article initially published infection research immunology research hiv-1-infected cells kolin mounts mature class-switched patient-derived xenograft models human immune responses innate immune responses springerlink instant access permissions human cytokines support human immune system human fetal liver hematopoietic stem cells human tumor xenograft immune system investigation cd34+ cell transplantation humanized csf-1 mice express human il-3 human monocyte subsets human hematopoietic cells mononuclear phagocyte system human allergy model privacy humanized mouse model optimal human t human viral infections engineering humanized mice melinda gates foundation present address competing financial interests antitumor immune modulators article rongvaux human nk cells support development neothy mouse model humanized mouse models including myeloid cells
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