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

By A. Rongvaux, T. Willinger, J. Martínek, T. Strowig, Sofia V. Gearty, L. Teichmann, Yasuyuki Saito, F. Marches, Stephanie Halene, A. Palucka and 2 more. Nature Biotechnology, 2014

715 citations recorded by the source corpus.

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.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/feafa854e3040f9ba5741d37b0fa9827412421b5

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In Immunology

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2. Hugo Gonzalez
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Citations in the corpus

• Phagocytosis: An Immunobiologic Process. (2016, background): “This pathway has been targeted to prevent clearance of human erythroid precursors in humanized mice (Rongvaux et al., 2014).”
• The fate and lifespan of human monocyte subsets in steady state and systemic inflammation (2017, methodology): “10 week-old MISTRG mice (Deng et al., 2015; Rongvaux et al., 2014) were used for adoptive transfer experiments described below.”
• Roles of the immune system in cancer: from tumor initiation to metastatic progression (2018, background): “In this model, irradiated immune-deficient mice are reconstituted with a human immune system (Rongvaux et al. 2014; Verma et al. 2017)).”