Novel Basophil- or Eosinophil-Depleted Mouse Models for Functional Analyses of Allergic Inflammation
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{"title"=>"Novel Basophil- or Eosinophil-Depleted Mouse Models for Functional Analyses of Allergic Inflammation", "type"=>"journal", "authors"=>[{"first_name"=>"Kunie", "last_name"=>"Matsuoka", "scopus_author_id"=>"55646013300"}, {"first_name"=>"Hiroshi", "last_name"=>"Shitara", "scopus_author_id"=>"6701812423"}, {"first_name"=>"Choji", "last_name"=>"Taya", "scopus_author_id"=>"6701592366"}, {"first_name"=>"Kenji", "last_name"=>"Kohno", "scopus_author_id"=>"7201467381"}, {"first_name"=>"Yoshiaki", "last_name"=>"Kikkawa", "scopus_author_id"=>"7102254532"}, {"first_name"=>"Hiromichi", "last_name"=>"Yonekawa", "scopus_author_id"=>"7007005605"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"368695825", "doi"=>"10.1371/journal.pone.0060958", "isbn"=>"1932-6203", "pmid"=>"23577180", "issn"=>"19326203", "scopus"=>"2-s2.0-84875994822", "sgr"=>"84875994822"}, "id"=>"49c6c4dd-a81f-3aff-94f3-8afafe7af341", "abstract"=>"Basophils and eosinophils play important roles in various host defense mechanisms but also act as harmful effectors in allergic disorders. We generated novel basophil- and eosinophil-depletion mouse models by introducing the human diphtheria toxin (DT) receptor gene under the control of the mouse CD203c and the eosinophil peroxidase promoter, respectively, to study the critical roles of these cells in the immunological response. These mice exhibited selective depletion of the target cells upon DT administration. In the basophil-depletion model, DT administration attenuated a drop in body temperature in IgG-mediated systemic anaphylaxis in a dose-dependent manner and almost completely abolished the development of ear swelling in IgE-mediated chronic allergic inflammation (IgE-CAI), a typical skin swelling reaction with massive eosinophil infiltration. In contrast, in the eosinophil-depletion model, DT administration ameliorated the ear swelling in IgE-CAI whether DT was administered before, simultaneously, or after, antigen challenge, with significantly lower numbers of eosinophils infiltrating into the swelling site. These results confirm that basophils and eosinophils act as the initiator and the effector, respectively, in IgE-CAI. In addition, antibody array analysis suggested that eotaxin-2 is a principal chemokine that attracts proinflammatory cells, leading to chronic allergic inflammation. Thus, the two mouse models established in this study are potentially useful and powerful tools for studying the in vivo roles of basophils and eosinophils. The combination of basophil- and eosinophil-depletion mouse models provides a new approach to understanding the complicated mechanism of allergic inflammation in conditions such as atopic dermatitis and asthma.", "link"=>"http://www.mendeley.com/research/novel-basophil-eosinophildepleted-mouse-models-functional-analyses-allergic-inflammation", "reader_count"=>28, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>1, "Researcher"=>10, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>1, "Researcher"=>10, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>12, "Medicine and Dentistry"=>4, "Immunology and Microbiology"=>8}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>8}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"United Kingdom"=>2, "Germany"=>2}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1018289"], "description"=>"<p>WT (A and B) and EoDTR (C and D) mice were treated once i.p. with 5 µg/kg DT at 2 days before and were injected i.v. with 300 µg TNP-specific IgE at 1 day before challenge with 10 µg TNP-OVA. Ear specimens prepared 4 days after antigen challenge were incubated with the CCR3-specific antibody, stained with DAB (brown), and counterstained with hematoxylin (blue). Scale bars = 50 µm. Data are representative of 6 independent experiments. (E) The number of eosinophils and other cells in a 100-µm square was counted. Data have been expressed in terms of mean ± SD and are representative of 3 repeated experiments. The <i>p</i> values of DT-treated EoDTR mice versus DT-treated WT mice are indicated. ***<i>p</i><0.005, **<i>p</i><0.001. Statistical analysis was performed using the Student’s <i>t</i> test.</p>", "links"=>[], "tags"=>["chronic-phase", "swelling", "ige-cai", "eodtr"], "article_id"=>677600, "categories"=>["Immunology"], "users"=>["Kunie Matsuoka", "Hiroshi Shitara", "Choji Taya", "Kenji Kohno", "Yoshiaki Kikkawa", "Hiromichi Yonekawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0060958.g007", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histopathological_analysis_of_the_ear_skin_in_chronic_phase_swelling_in_IgE_CAI_in_EoDTR_mice_/677600", "title"=>"Histopathological analysis of the ear skin in chronic-phase swelling in IgE-CAI in EoDTR mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-08 02:06:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/1018283"], "description"=>"<p>(A) The <i>alb</i> promoter of the original TRECK cassette was replaced with the <i>EPO</i> promoter to identify the exclusive expression of hDTR on eosinophils <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060958#pone.0060958-Saito1\" target=\"_blank\">[29]</a>. (B) Cytospin slides of the peripheral leukocytes of EoDTR mice were stained with antibodies against hDTR (green), CCR3 (red), and DAPI (nuclei, blue). Scale bar = 20 µm. (C) EoDTR and WT mice were treated once i.p. with DT (5 µg/kg body weight). After 3 days, eosinophils in the peripheral blood, spleen, and bone marrow were analyzed by flow cytometry. The percentage of eosinophils (CCR3<sup>+</sup>Siglec-F<sup>+</sup>) is indicated.</p>", "links"=>[], "tags"=>["eodtr", "mice", "selective", "inducible", "ablation"], "article_id"=>677594, "categories"=>["Immunology"], "users"=>["Kunie Matsuoka", "Hiroshi Shitara", "Choji Taya", "Kenji Kohno", "Yoshiaki Kikkawa", "Hiromichi Yonekawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0060958.g005", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Generation_of_EoDTR_mice_for_the_selective_and_inducible_ablation_of_eosinophils_/677594", "title"=>"Generation of EoDTR mice for the selective and inducible ablation of eosinophils.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-08 02:06:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/1018278"], "description"=>"<p>(A) BasoDTR (n = 4) and WT mice (n = 4) were treated once i.p. with 25 µg/kg DT or with PBS 2 days before and were injected i.v. with 300 µg TNP-specific IgE 1 day before challenge with 10 µg TNP-OVA. Ear thickness was measured at the indicated time points. The kinetics of changes in ear thickness after antigen challenge are shown. Data have been expressed as mean ± SEM and are representative of 4 repeated experiments. <i>P</i> values of DT-administered BasoDTR mice versus WT mice are indicated. *<i>p</i><0.05, **<i>p</i><0.01. (B) WT and BasoDTR mice were passively sensitized with i.v. injections of 200 µl diluted ascites containing 300 µg of TNP-specific IgE at 1 day before 50 µg of TNP<sub>13</sub>-OVA was administered. The change in rectal temperature over time after allergen challenge is shown. Data have been expressed as mean ± SEM and are representative of 4 repeated experiments. (C) The ears of WT (n = 4), BasoDTR (n = 4), and EoDTR (n = 4) mice were excised and homogenized in PBS at 4 days after antigen challenge. The major cytokines and chemokines in 200 µg of extracted total proteins were analyzed semiquantitatively by using antibody arrays. Relative concentrations have been indicated in terms of mean ± SEM. The <i>p</i> values of BasoDTR mice versus WT mice and of EoDTR mice versus WT mice are indicated. *<i>p</i><0.05, **<i>p</i><0.01. Statistical analysis was performed using the Student’s <i>t</i> test.</p>", "links"=>[], "tags"=>["cytokines", "chemokines", "antigen-challenged"], "article_id"=>677589, "categories"=>["Immunology"], "users"=>["Kunie Matsuoka", "Hiroshi Shitara", "Choji Taya", "Kenji Kohno", "Yoshiaki Kikkawa", "Hiromichi Yonekawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0060958.g003", "stats"=>{"downloads"=>5, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IgE_CAI_and_the_expression_of_cytokines_and_chemokines_in_antigen_challenged_ears_/677589", "title"=>"IgE-CAI and the expression of cytokines and chemokines in antigen-challenged ears.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-08 02:06:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/1018292"], "description"=>"<p>Three WT and EoDTR mice were i.p. administered 5 µg/kg DT. After 3 d, FACS analysis of peripheral blood cells was performed. The percentages of the indicated cells from the total cells have been shown as mean ± SD values.</p>", "links"=>[], "tags"=>["leukocytes", "peripheral", "dt"], "article_id"=>677603, "categories"=>["Immunology"], "users"=>["Kunie Matsuoka", "Hiroshi Shitara", "Choji Taya", "Kenji Kohno", "Yoshiaki Kikkawa", "Hiromichi Yonekawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0060958.t002", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Percentage_of_leukocytes_in_peripheral_blood_after_DT_administration_/677603", "title"=>"Percentage of leukocytes in peripheral blood after DT administration.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-04-08 02:06:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1018277"], "description"=>"<p>BasoDTR and WT mice were treated once i.p. with DT (50 µg/kg body weight). After 4 days, basophils in the peripheral blood (A), spleen (B), bone marrow (C), and peritoneal mast cells (D) were analyzed by flow cytometry. The percentages of basophils (IgE<sup>+</sup>CD49b<sup>+</sup>) and mast cells (IgE<sup>+</sup>c-kit<sup>+</sup>) are indicated.</p>", "links"=>[], "tags"=>["ablation", "dt", "basodtr"], "article_id"=>677588, "categories"=>["Immunology"], "users"=>["Kunie Matsuoka", "Hiroshi Shitara", "Choji Taya", "Kenji Kohno", "Yoshiaki Kikkawa", "Hiromichi Yonekawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0060958.g002", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Basophil_specific_ablation_after_DT_administration_in_BasoDTR_mice_/677588", "title"=>"Basophil-specific ablation after DT administration in BasoDTR mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-08 02:06:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/1018291"], "description"=>"<p>Three WT and BasoDTR mice were i.p. administered 50 µg/kg DT. After 4 days, FACS analysis of peripheral blood cells and peritoneal exudate cells was performed. The percentages of the indicated cells from the total cells have been shown as mean ± SD values.</p>", "links"=>[], "tags"=>["leukocytes", "peripheral", "mast", "cells", "peritoneal", "exudate"], "article_id"=>677602, "categories"=>["Immunology"], "users"=>["Kunie Matsuoka", "Hiroshi Shitara", "Choji Taya", "Kenji Kohno", "Yoshiaki Kikkawa", "Hiromichi Yonekawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0060958.t001", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Percentage_of_leukocytes_in_peripheral_blood_and_mast_cells_in_peritoneal_exudate_cells_/677602", "title"=>"Percentage of leukocytes in peripheral blood and mast cells in peritoneal exudate cells.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-04-08 02:06:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1018285"], "description"=>"<p>Ear swelling in IgE-CAI in mice receiving PBS (A, n = 5) or 5 µg/kg of DT at 2 days before (B, n = 5), at the same time as (C, n = 7), or 2 days after (D, n = 6) the antigen challenge were measured at the indicated time points. Data have been expressed in terms of mean ± SEM and are representative of 2 repeated experiments. The <i>p</i> values of DT-treated EoDTR mice versus DT-treated WT mice are indicated. *<i>p</i><0.05, **<i>p</i><0.01. Statistical analysis was performed using the Student’s <i>t</i> test.</p>", "links"=>[], "tags"=>["eodtr"], "article_id"=>677596, "categories"=>["Immunology"], "users"=>["Kunie Matsuoka", "Hiroshi Shitara", "Choji Taya", "Kenji Kohno", "Yoshiaki Kikkawa", "Hiromichi Yonekawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0060958.g006", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IgE_CAI_in_EoDTR_mice_/677596", "title"=>"IgE-CAI in EoDTR mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-08 02:06:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/1018280"], "description"=>"<p>(A) BasoDTR mice (n = 4 per group) were treated once i.p. with 25 or 50 µg/kg of DT or PBS at 4 days prior to and were i.v. injected with 500 µg rat anti-FcγRII/III (2.4G2) antibodies in 200 µl PBS. Body temperature was measured at the indicated time points. Data have been expressed as mean ± SEM and are representative of 4 repeated experiments. The <i>p</i> values of DT-administered mice versus control mice are indicated. *<i>p</i><0.05, **<i>p</i><0.01. (B) The maximum decrease in the body temperature of BasoDTR and WT mice (n = 4 per group) with or without DT treatment were compared. Data have been expressed in terms of mean ± SEM and are representative of 4 repeated experiments. *<i>p</i><0.05. Statistical analysis was performed using the Student’s <i>t</i> test.</p>", "links"=>[], "tags"=>["systemic", "anaphylaxis", "basodtr"], "article_id"=>677591, "categories"=>["Immunology"], "users"=>["Kunie Matsuoka", "Hiroshi Shitara", "Choji Taya", "Kenji Kohno", "Yoshiaki Kikkawa", "Hiromichi Yonekawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0060958.g004", "stats"=>{"downloads"=>2, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IgG_mediated_systemic_anaphylaxis_decreased_in_BasoDTR_mice_/677591", "title"=>"IgG-mediated systemic anaphylaxis decreased in BasoDTR mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-08 02:06:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1018293"], "description"=>"<div><p>Basophils and eosinophils play important roles in various host defense mechanisms but also act as harmful effectors in allergic disorders. We generated novel basophil- and eosinophil-depletion mouse models by introducing the human diphtheria toxin (DT) receptor gene under the control of the mouse CD203c and the eosinophil peroxidase promoter, respectively, to study the critical roles of these cells in the immunological response. These mice exhibited selective depletion of the target cells upon DT administration. In the basophil-depletion model, DT administration attenuated a drop in body temperature in IgG-mediated systemic anaphylaxis in a dose-dependent manner and almost completely abolished the development of ear swelling in IgE-mediated chronic allergic inflammation (IgE-CAI), a typical skin swelling reaction with massive eosinophil infiltration. In contrast, in the eosinophil-depletion model, DT administration ameliorated the ear swelling in IgE-CAI whether DT was administered before, simultaneously, or after, antigen challenge, with significantly lower numbers of eosinophils infiltrating into the swelling site. These results confirm that basophils and eosinophils act as the initiator and the effector, respectively, in IgE-CAI. In addition, antibody array analysis suggested that eotaxin-2 is a principal chemokine that attracts proinflammatory cells, leading to chronic allergic inflammation. Thus, the two mouse models established in this study are potentially useful and powerful tools for studying the <i>in vivo</i> roles of basophils and eosinophils. The combination of basophil- and eosinophil-depletion mouse models provides a new approach to understanding the complicated mechanism of allergic inflammation in conditions such as atopic dermatitis and asthma.</p> </div>", "links"=>[], "tags"=>["basophil-", "eosinophil-depleted", "allergic"], "article_id"=>677604, "categories"=>["Immunology"], "users"=>["Kunie Matsuoka", "Hiroshi Shitara", "Choji Taya", "Kenji Kohno", "Yoshiaki Kikkawa", "Hiromichi Yonekawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0060958", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Novel_Basophil_or_Eosinophil_Depleted_Mouse_Models_for_Functional_Analyses_of_Allergic_Inflammation_/677604", "title"=>"Novel Basophil- or Eosinophil-Depleted Mouse Models for Functional Analyses of Allergic Inflammation", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-08 02:06:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/1018275"], "description"=>"<p>(A) Construct of a transgene for BasoDTR mice. The <i>alb</i> promoter of the original TRECK cassette was replaced with the <i>CD203c</i> promoter to allow the exclusive expression of hDTR on basophils <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060958#pone.0060958-Saito1\" target=\"_blank\">[29]</a>. (B) Basophils were purified as IgE-positive cells from the peripheral blood of BasoDTR and WT mice by using the MACS system. RT-PCR analysis was performed to examine the specific expression of hDTR mRNA in basophils. (C) Cytospin slides of the peripheral leukocytes of BasoDTR mice were stained with antibodies against hDTR (green), IgE (red), and DAPI (nuclei, blue). Scale bar = 20 µm.</p>", "links"=>[], "tags"=>["basodtr", "mice", "selective", "inducible", "ablation"], "article_id"=>677586, "categories"=>["Immunology"], "users"=>["Kunie Matsuoka", "Hiroshi Shitara", "Choji Taya", "Kenji Kohno", "Yoshiaki Kikkawa", "Hiromichi Yonekawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0060958.g001", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Generation_of_BasoDTR_mice_for_the_selective_and_inducible_ablation_of_basophils_/677586", "title"=>"Generation of BasoDTR mice for the selective and inducible ablation of basophils.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-08 02:06:26"}

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Relative Metric

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