A novel Flt3‐deficient HIS mouse model with selective enhancement of human DC development

Li, Yan; Mention, Jean–Jacques; Court, Nathalie; Masse‐Ranson, Guillemette; Toubert, Antoine; Spits, Hergen; Legrand, Nicolas; Corcuff, Erwan; Strick‐Marchand, Hélène; Santo, James P. Di

doi:10.1002/eji.201546132

Cited by 63 publications

(60 citation statements)

References 34 publications

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“…Consistent with previous studies, 26,[28][29][30][31] we found that exogenous Flt3L treatment could significantly boost human myeloid cell development in BRGSF HIS mice (Figure 1). We examined 4 human CD3 2 CD19 2 NKp46 2 HLA-DR 1 myeloid subpopulations: CD14 1 monocytes, CD123 1 plasmacytoid DCs (pDCs), CD141/ BDCA-3 1 cDCs, and CD1c/BDCA-1 1 cDCs.…”

Section: Resultssupporting

confidence: 92%

“…Exogenous Flt3L had no effect on the Flt3-deficient mouse myeloid cells (data not shown), thereby allowing a selective boost of human myeloid cells in this context. Compared with previous studies using BRGF recipients, 26 we found a quantitatively stronger effect in the absolute numbers that was further extrapolated to CD14 1 monocytes and localized not only in spleen but systemically.…”

Section: Resultscontrasting

confidence: 75%

“…We have previously described BRGF recipients that offer an approach to enhance human DC homeostasis in HIS mice 26 and characterized the BALB/c Rag2 2/2 Il2rg 2/2 Sirpa NOD strain with enhanced human hematopoietic engraftment resulting from improved macrophage tolerance of human cells. 15 We combined these 2 models to create the BRGSF strain and analyzed HIS mice after intrahepatic transfer of human CD34…”

Section: Resultsmentioning

confidence: 99%

“…Given previous studies demonstrating the effect of DC cross talk in promoting NK cell maturation and proliferation, 24,26 we tested whether Flt3L-dependent enhancement of myeloid cell development in BRGSF HIS mice affected the phenotype and function of conventional NK cells (defined as CD3 2 NKp46 1 CD94 1 cells). Administration of Flt3L to BRGSF mice led to an increase in frequency and absolute number (2-to 2.5-fold) of conventional NK cells in the liver, spleen, and lung (Figures 2A,B Figure 2C).…”

Section: Lymphocyte Development In Flt3l-treated Brgsf His Micementioning

confidence: 99%

“…[22][23][24][25] We recently reported a humanized mouse model in which Flt3L-mediated enhancement of human DC numbers resulted in improved human NK cell homeostasis. 26 In this report, we generate and characterize a novel BALB/c Rag2…”

Section: Introductionmentioning

confidence: 99%

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A functional DC cross talk promotes human ILC homeostasis in humanized mice

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Section: Resultssupporting

confidence: 92%

Section: Resultscontrasting

confidence: 75%

Section: Resultsmentioning

confidence: 99%

Section: Lymphocyte Development In Flt3l-treated Brgsf His Micementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A functional DC cross talk promotes human ILC homeostasis in humanized mice

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Against all odds: The road to success in the development of human immune reconstitution mice

Bin,

Ren,

Zhang

et al. 2024

Anim Models and Exp Med

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The mouse genome has a high degree of homology with the human genome, and its physiological, biochemical, and developmental regulation mechanisms are similar to those of humans; therefore, mice are widely used as experimental animals. However, it is undeniable that interspecies differences between humans and mice can lead to experimental errors. The differences in the immune system have become an important factor limiting current immunological research. The application of immunodeficient mice provides a possible solution to these problems. By transplanting human immune cells or tissues, such as peripheral blood mononuclear cells or hematopoietic stem cells, into immunodeficient mice, a human immune system can be reconstituted in the mouse body, and the engrafted immune cells can elicit human‐specific immune responses. Researchers have been actively exploring the development and differentiation conditions of host recipient animals and grafts in order to achieve better immune reconstitution. Through genetic engineering methods, immunodeficient mice can be further modified to provide a favorable developmental and differentiation microenvironment for the grafts. From initially only being able to reconstruct single T lymphocyte lineages, it is now possible to reconstruct lymphoid and myeloid cells, providing important research tools for immunology‐related studies. In this review, we compare the differences in immune systems of humans and mice, describe the development history of human immune reconstitution from the perspectives of immunodeficient mice and grafts, and discuss the latest advances in enhancing the efficiency of human immune cell reconstitution, aiming to provide important references for immunological related researches.

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Humanized Mouse Models for Immuno‐oncology Drug Discovery

Kumari¹,

Feuer²,

Bourré³

2023

Current Protocols

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Breakthroughs in cancer treatment with immunotherapeutics have provided long‐term patient benefits for many different types of cancer. However, complete response is not achieved in many patients and tumor types, and the mechanisms underlying this lack of response are poorly understood. Despite this, numerous new targets, therapeutics, and drug combinations are being developed and tested in clinical trials. Preclinical models that recapitulate the complex human tumor microenvironment and the interplay between tumor and immune cells within the cancer‐immunity cycle are needed to improve our understanding and screen new therapeutics for efficacy and safety/toxicity. Humanized mice, encompassing human tumors and human immune cells engrafted on immunodeficient mice, have been widely used for many years in immuno‐oncology, with developments to improve both the humanization and the translational value central to the next generation of models. In this overview, we discuss recent advances in humanized models relevant to immuno‐oncology drug discovery, the advantages and limitations of such models, the application of humanized models for efficacy and safety assessments of immunotherapeutics, and the potential opportunities. © 2023 Crown Bioscience. Current Protocols published by Wiley Periodicals LLC.

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A novel Flt3‐deficient HIS mouse model with selective enhancement of human DC development

Cited by 63 publications

References 34 publications

A functional DC cross talk promotes human ILC homeostasis in humanized mice

A functional DC cross talk promotes human ILC homeostasis in humanized mice

Against all odds: The road to success in the development of human immune reconstitution mice

Humanized Mouse Models for Immuno‐oncology Drug Discovery

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