title: 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.
authors.affiliation: 1] Department of Immunobiology, Yale University, New Haven, Connecticut, USA. [2].
authors.forename: Anthony
authors.initials: A
authors.lastname: Rongvaux
authors.affiliation: 1] Department of Immunobiology, Yale University, New Haven, Connecticut, USA. [2].
authors.forename: Tim
authors.initials: T
authors.lastname: Willinger
authors.affiliation: 1] Baylor Institute for Immunology Research, Dallas, Texas, USA. [2] Biomedical studies program, Baylor University, Waco, Texas, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Martinek
authors.affiliation: 1] Department of Immunobiology, Yale University, New Haven, Connecticut, USA. [2].
authors.forename: Till
authors.initials: T
authors.lastname: Strowig
authors.affiliation: Department of Immunobiology, Yale University, New Haven, Connecticut, USA.
authors.forename: Sofia V
authors.initials: SV
authors.lastname: Gearty
authors.affiliation: 1] Department of Laboratory Medicine, Yale University, New Haven, Connecticut, USA. [2] Department of Medicine III, University Hospital Bonn, Bonn, Germany.
authors.forename: Lino L
authors.initials: LL
authors.lastname: Teichmann
authors.affiliation: Division of Hematology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Baylor Institute for Immunology Research, Dallas, Texas, USA.
authors.forename: Florentina
authors.initials: F
authors.lastname: Marches
authors.affiliation: Section of Hematology, Department of Internal Medicine and Yale Comprehensive Cancer Center, Yale University, New Haven, Connecticut, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Halene
authors.affiliation: Baylor Institute for Immunology Research, Dallas, Texas, USA.
authors.forename: A Karolina
authors.initials: AK
authors.lastname: Palucka
authors.affiliation: Division of Hematology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Markus G
authors.initials: MG
authors.lastname: Manz
authors.affiliation: 1] Department of Immunobiology, Yale University, New Haven, Connecticut, USA. [2] Howard Hughes Medical Institute, Yale University, New Haven, Connecticut, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
mesh_terms: D000818:Animals; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics* / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology / Q000502:physiology; D017254:Leukemic Infiltration / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000276:immunology / Q000502:physiology; D009374:Neoplasms, Experimental; D014183:Transplantation, Heterologous