A humanized mouse model to study asthmatic airway inflammation via the human IL-33/IL-13 axis

Ito, Ryoji; Maruoka, Shuichiro; Soda, Kaori; Katano, Ikumi; Kawai, Kenji; Yagoto, Mika; Hanazawa, Asami; Takahashi, Takeshi; Ogura, Tomoyuki; Goto, Motohito; Takahashi, Riichi; Toyoshima, Shota; Okayama, Yoshimichi; Izuhara, Kenji; Gon, Yasuhiro; Hashimoto, Shigeo; Ito, Mamoru; Nunomura, Satoshi

doi:10.1172/jci.insight.121580

Cited by 38 publications

(27 citation statements)

References 57 publications

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“…A new model of humanized mice called NSG-SGM3 was able to express functional human Treg, T and B cells, myeloid progenitor, and dendritic cells and mast cells (22,(35)(36)(37)(38). NSG-SGM3 HDMinduced asthma model is known to exhibit elevated AHR, a bronchial infiltrate and alteration associated with Th2 inflammation (39). For the first time, we developed a model of HDM-induced allergic severe asthma in NSG-SGM3 humanized mice.…”

Section: Discussionmentioning

confidence: 99%

Der p 2.1 Peptide Abrogates House Dust Mites-Induced Asthma Features in Mice and Humanized Mice by Inhibiting DC-Mediated T Cell Polarization

et al. 2020

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Section: Discussionmentioning

confidence: 99%

Der p 2.1 Peptide Abrogates House Dust Mites-Induced Asthma Features in Mice and Humanized Mice by Inhibiting DC-Mediated T Cell Polarization

et al. 2020

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“…IL-33 induces an asthma-like phenotype in Rag2 −/− mice, which lack mature lymphocytes, demonstrating that adaptive immune responses are not required to induce an asthma-like phenotype (139). Further, in a new humanized mouse model (NOG IL-3/GM-CSF), administration of human IL-33 induced an asthma-like phenotype mediated by human IL-13 (140). The main producers of IL-13 in this setting were T cells and mast cells.…”

Section: Ige-independent Activation Of Mast Cells In Asthmamentioning

confidence: 99%

Mast Cells and Their Progenitors in Allergic Asthma

2019

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Mast cells and their mediators have been implicated in the pathogenesis of asthma and allergy for decades. Allergic asthma is a complex chronic lung disease in which several different immune cells, genetic factors and environmental exposures influence the pathology. Mast cells are key players in the asthmatic response through secretion of a multitude of mediators with pro-inflammatory and airway-constrictive effects. Well-known mast cell mediators, such as histamine and bioactive lipids are responsible for many of the physiological effects observed in the acute phase of allergic reactions. The accumulation of mast cells at particular sites of the allergic lung is likely relevant to the asthma phenotype, severity and progression. Mast cells located in different compartments in the lung and airways have different characteristics and express different mediators. According to in vivo experiments in mice, lung mast cells develop from mast cell progenitors induced by inflammatory stimuli to migrate to the airways. Human mast cell progenitors have been identified in the blood circulation. A high frequency of circulating human mast cell progenitors may reflect ongoing pathological changes in the allergic lung. In allergic asthma, mast cells become activated mainly via IgE-mediated crosslinking of the high affinity receptor for IgE (FcεRI) with allergens. However, mast cells can also be activated by numerous other stimuli e.g. toll-like receptors and MAS-related G protein-coupled receptor X2. In this review, we summarize research with implications on the role and development of mast cells and their progenitors in allergic asthma and cover selected activation pathways and mast cell mediators that have been implicated in the pathogenesis. The review places an emphasis on describing mechanisms identified using in vivo mouse models and data obtained by analysis of clinical samples.

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“…These new models have enabled a multitude of new findings in the field of asthma research such as the interaction of allergen immunotherapy, clinical tolerance and cellular response, as well as new therapeutic options through the induction of peripheral tolerance by sGARP (glycoprotein A repetitions predominant) (114,115). New mechanistic relationships were also clarified, such as the influence of the IL-33/IL-13 axis on the asthmatic airway inflammation or the anti-inflammatory effect of IL-35 in asthmatic diseases (116). Based on the immunodeficient IL2rg null mouse, further mouse models emerged, including the Hu-SRC-SCID mouse and the BLT mouse as well as the Hu-PBL-SCID mouse providing further insight into our understanding of the development of AHR as a characteristic feature of allergic asthma (117) and discovery of new therapeutics, such as the use of TIM-1 antagonists as a possible treatment strategy for asthma (118).…”

Section: Humanized Mouse Modelsmentioning

confidence: 99%

Mimicking Antigen-Driven Asthma in Rodent Models—How Close Can We Get?

et al. 2020

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Asthma is a heterogeneous disease with increasing prevalence worldwide characterized by chronic airway inflammation, increased mucus secretion and bronchial hyperresponsiveness. The phenotypic heterogeneity among asthmatic patients is accompanied by different endotypes, mainly Type 2 or non-Type 2. To investigate the pathomechanism of this complex disease many animal models have been developed, each trying to mimic specific aspects of the human disease. Rodents have classically been employed in animal models of asthma. The present review provides an overview of currently used Type 2 vs. non-Type 2 rodent asthma models, both acute and chronic. It further assesses the methods used to simulate disease development and exacerbations as well as to quantify allergic airway inflammation, including lung physiologic, cellular and molecular immunologic responses. Furthermore, the employment of genetically modified animals, which provide an in-depth understanding of the role of a variety of molecules, signaling pathways and receptors implicated in the development of this disease as well as humanized models of allergic inflammation, which have been recently developed to overcome differences between the rodent and human immune systems, are discussed. Nevertheless, differences between mice and humans should be carefully considered and limits of extrapolation should be wisely taken into account when translating experimental results into clinical use.

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A humanized mouse model to study asthmatic airway inflammation via the human IL-33/IL-13 axis

Cited by 38 publications

References 57 publications

Der p 2.1 Peptide Abrogates House Dust Mites-Induced Asthma Features in Mice and Humanized Mice by Inhibiting DC-Mediated T Cell Polarization

Der p 2.1 Peptide Abrogates House Dust Mites-Induced Asthma Features in Mice and Humanized Mice by Inhibiting DC-Mediated T Cell Polarization

Mast Cells and Their Progenitors in Allergic Asthma

Mimicking Antigen-Driven Asthma in Rodent Models—How Close Can We Get?

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