NOD-scid IL2R γ<sup>null</sup> mice engrafted with human peripheral blood mononuclear cells as a model to test therapeutics targeting human signaling pathways
<p>Abstract</p> <p>Background</p> <p>Animal models of human inflammatory diseases have limited predictive quality for human clinical trials for various reasons including species specific activation mechanisms and the immunological background of the animals which markedl...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2013-01-01
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| Series: | Journal of Translational Medicine |
| Online Access: | http://www.translational-medicine.com/content/11/1/4 |
| _version_ | 1811287328133480448 |
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| author | Zadeh-Khorasani Maryam Nolte Thomas Mueller Thomas D Pechlivanis Markos Rueff Franziska Wollenberg Andreas Fricker Gert Wolf Eckhard Siebeck Matthias Gropp Roswitha |
| author_facet | Zadeh-Khorasani Maryam Nolte Thomas Mueller Thomas D Pechlivanis Markos Rueff Franziska Wollenberg Andreas Fricker Gert Wolf Eckhard Siebeck Matthias Gropp Roswitha |
| author_sort | Zadeh-Khorasani Maryam |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Animal models of human inflammatory diseases have limited predictive quality for human clinical trials for various reasons including species specific activation mechanisms and the immunological background of the animals which markedly differs from the genetically heterogeneous and often aged patient population.</p> <p>Objective</p> <p>Development of an animal model allowing for testing therapeutics targeting pathways involved in the development of Atopic Dermatitis (AD) with better translatability to the patient.</p> <p>Methods</p> <p>NOD-scid IL2R γ<sup>null</sup> mice engrafted with human peripheral blood mononuclear cells (hPBMC) derived from patients suffering from AD and healthy volunteers were treated with IL-4 and the antagonistic IL-4 variant R121/Y124D (Pitrakinra). Levels of human (h)IgE, amount of B-, T- and plasma- cells and ratio of CD4 : CD8 positive cells served as read out for induction and inhibition of cell proliferation and hIgE secretion. Results were compared to <it>in vitro</it> analysis.</p> <p>Results</p> <p>hIgE secretion was induced by IL-4 and inhibited by the IL-4 antagonist Pitrakinra <it>in vivo</it> when formulated with methylcellulose. B-cells proliferated in response to IL-4 <it>in vivo</it>; the effect was abrogated by Pitrakinra. IL-4 shifted CD4 : CD8 ratios <it>in vitro</it> and <it>in vivo</it> when hPBMC derived from healthy volunteers were used. Pitrakinra reversed the effect. Human PBMC derived from patients with AD remained inert and engrafted mice reflected the individual responses observed <it>in vitro</it>.</p> <p>Conclusion</p> <p>NOD-scid IL2R γ<sup>null</sup> mice engrafted with human PBMC reflect the immunological history of the donors and provide a complementary tool to <it>in vitro</it> studies. Thus, studies in this model might provide data with better translatability from bench to bedside.</p> |
| first_indexed | 2024-04-13T03:16:41Z |
| format | Article |
| id | doaj.art-9f222f811960468498039214f4a7e7f6 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-13T03:16:41Z |
| publishDate | 2013-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-9f222f811960468498039214f4a7e7f62022-12-22T03:04:54ZengBMCJournal of Translational Medicine1479-58762013-01-01111410.1186/1479-5876-11-4NOD-scid IL2R γ<sup>null</sup> mice engrafted with human peripheral blood mononuclear cells as a model to test therapeutics targeting human signaling pathwaysZadeh-Khorasani MaryamNolte ThomasMueller Thomas DPechlivanis MarkosRueff FranziskaWollenberg AndreasFricker GertWolf EckhardSiebeck MatthiasGropp Roswitha<p>Abstract</p> <p>Background</p> <p>Animal models of human inflammatory diseases have limited predictive quality for human clinical trials for various reasons including species specific activation mechanisms and the immunological background of the animals which markedly differs from the genetically heterogeneous and often aged patient population.</p> <p>Objective</p> <p>Development of an animal model allowing for testing therapeutics targeting pathways involved in the development of Atopic Dermatitis (AD) with better translatability to the patient.</p> <p>Methods</p> <p>NOD-scid IL2R γ<sup>null</sup> mice engrafted with human peripheral blood mononuclear cells (hPBMC) derived from patients suffering from AD and healthy volunteers were treated with IL-4 and the antagonistic IL-4 variant R121/Y124D (Pitrakinra). Levels of human (h)IgE, amount of B-, T- and plasma- cells and ratio of CD4 : CD8 positive cells served as read out for induction and inhibition of cell proliferation and hIgE secretion. Results were compared to <it>in vitro</it> analysis.</p> <p>Results</p> <p>hIgE secretion was induced by IL-4 and inhibited by the IL-4 antagonist Pitrakinra <it>in vivo</it> when formulated with methylcellulose. B-cells proliferated in response to IL-4 <it>in vivo</it>; the effect was abrogated by Pitrakinra. IL-4 shifted CD4 : CD8 ratios <it>in vitro</it> and <it>in vivo</it> when hPBMC derived from healthy volunteers were used. Pitrakinra reversed the effect. Human PBMC derived from patients with AD remained inert and engrafted mice reflected the individual responses observed <it>in vitro</it>.</p> <p>Conclusion</p> <p>NOD-scid IL2R γ<sup>null</sup> mice engrafted with human PBMC reflect the immunological history of the donors and provide a complementary tool to <it>in vitro</it> studies. Thus, studies in this model might provide data with better translatability from bench to bedside.</p>http://www.translational-medicine.com/content/11/1/4 |
| spellingShingle | Zadeh-Khorasani Maryam Nolte Thomas Mueller Thomas D Pechlivanis Markos Rueff Franziska Wollenberg Andreas Fricker Gert Wolf Eckhard Siebeck Matthias Gropp Roswitha NOD-scid IL2R γ<sup>null</sup> mice engrafted with human peripheral blood mononuclear cells as a model to test therapeutics targeting human signaling pathways Journal of Translational Medicine |
| title | NOD-scid IL2R γ<sup>null</sup> mice engrafted with human peripheral blood mononuclear cells as a model to test therapeutics targeting human signaling pathways |
| title_full | NOD-scid IL2R γ<sup>null</sup> mice engrafted with human peripheral blood mononuclear cells as a model to test therapeutics targeting human signaling pathways |
| title_fullStr | NOD-scid IL2R γ<sup>null</sup> mice engrafted with human peripheral blood mononuclear cells as a model to test therapeutics targeting human signaling pathways |
| title_full_unstemmed | NOD-scid IL2R γ<sup>null</sup> mice engrafted with human peripheral blood mononuclear cells as a model to test therapeutics targeting human signaling pathways |
| title_short | NOD-scid IL2R γ<sup>null</sup> mice engrafted with human peripheral blood mononuclear cells as a model to test therapeutics targeting human signaling pathways |
| title_sort | nod scid il2r γ sup null sup mice engrafted with human peripheral blood mononuclear cells as a model to test therapeutics targeting human signaling pathways |
| url | http://www.translational-medicine.com/content/11/1/4 |
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