Abstract
Human immune system mice, also referred to as humanized mice, are a major research tool for the in vivo study of human immune system function. Upon reconstitution with human hematopoietic stem cells, all major human leukocyte populations develop in immunodeficient mice and can be detected in peripheral blood as well as in lymphatic and nonlymphatic tissue. This includes human macrophages that are intrinsically difficult to study from humans due to their organ-resident nature. In the following chapter, we provide a detailed protocol for generation of human immune system mice. We suggest that these mice are a suitable model to study human macrophage function in vivo.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Lux A, Nimmerjahn F (2013) Of mice and men: the need for humanized mouse models to study human IgG activity in vivo. J Clin Immunol 33(1):4–8
Shultz LD, Ishikawa F, Greiner DL (2007) Humanized mice in translational biomedical research. Nat Rev Immunol 7(2):118–130
Schinnerling K et al (2019) Humanized mouse models of rheumatoid arthritis for studies on immunopathogenesis and preclinical testing of cell-based therapies. Front Immunol 10:203
Schwab I, Lux A, Nimmerjahn F (2015) Pathways responsible for human autoantibody and therapeutic intravenous IgG activity in humanized mice. Cell Rep 13(3):610–620
Martinov T et al (2021) Building the next generation of humanized hemato-lymphoid system mice. Front Immunol 12:643852
Miao M et al (2021) Reevaluation of NOD/SCID mice as NK cell-deficient models. Biomed Res Int 2021:8851986
Shultz LD et al (1995) Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice. J Immunol 154(1):180–191
Zhou Q et al (2014) Humanized NOD-SCID IL2rg–/– mice as a preclinical model for cancer research and its potential use for individualized cancer therapies. Cancer Lett 344(1):13–19
Ito M et al (2002) NOD/SCID/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells. Blood 100(9):3175–3182
Lux A et al (2014) A humanized mouse identifies the bone marrow as a niche with low therapeutic IgG activity. Cell Rep 7(1):236–248
Rongvaux A et al (2014) Development and function of human innate immune cells in a humanized mouse model. Nat Biotechnol 32(4):364–372
Evren E et al (2021) Distinct developmental pathways from blood monocytes generate human lung macrophage diversity. Immunity 54(2):259–275.e7
Evren E et al (2022) CD116+ fetal precursors migrate to the perinatal lung and give rise to human alveolar macrophages. J Exp Med 219(2)
Nimmerjahn F et al (2015) FcgR dependent mechanisms of cytotoxic, agonistic, and neutralizing antibody activities. Trends Immunol 36(6):325–336
Dekkers G et al (2017) Affinity of human IgG subclasses to mouse Fc gamma receptors. MAbs 9(5):767–773
Brandsma AM et al (2016) Clarifying the confusion between cytokine and Fc receptor “common gamma chain”. Immunity 45(2):225–226
Danzer H et al (2020) Human Fcγ-receptor IIb modulates pathogen-specific versus self-reactive antibody responses in Lyme arthritis. elife 9
Baerenwaldt A et al (2011) Fcγ receptor IIB (FcγRIIB) maintains humoral tolerance in the human immune system in vivo. Proc Natl Acad Sci U S A 108(46):18772–18777
Boyette LB et al (2017) Phenotype, function, and differentiation potential of human monocyte subsets. PLoS One 12(4):e0176460
Genin M et al (2015) M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide. BMC Cancer 15:577
Larionova I et al (2020) Tumor-associated macrophages in human breast, colorectal, lung, ovarian and prostate cancers. Front Oncol 10:566511
Acknowledgments
This work was supported by German Research Foundation (DFG) grants SFB1526 and FOR2886 to A.L.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2024 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Voss, L., Reitinger, C., Lux, A. (2024). Phenotyping of Macrophages in Human Immune System Mice. In: Mass, E. (eds) Tissue-Resident Macrophages. Methods in Molecular Biology, vol 2713. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3437-0_7
Download citation
DOI: https://doi.org/10.1007/978-1-0716-3437-0_7
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-3436-3
Online ISBN: 978-1-0716-3437-0
eBook Packages: Springer Protocols