Modifying Graft-versus-Host Disease in a Humanized Mouse Model by Targeting Macrophages or B-Cells
Humanized mouse models can well be modified to study specific aspects of Graft-versus-Host Disease (GvHD). This paper shows the results of both macrophage depletion and (early) B-cell depletion in a humanized mouse model using RAG2-/-γc-/- mice injected with HuPBMCs. Macrophage depletion showed a si...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2019/3538963 |
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| author | Marieke C. H. Hogenes Suzanne van Dorp Joyce van Kuik Filipa R. P. Monteiro Natalie ter Hoeve Liane Guedes Marijke R. van Dijk Anton C. Martens Roel A. de Weger |
| author_facet | Marieke C. H. Hogenes Suzanne van Dorp Joyce van Kuik Filipa R. P. Monteiro Natalie ter Hoeve Liane Guedes Marijke R. van Dijk Anton C. Martens Roel A. de Weger |
| author_sort | Marieke C. H. Hogenes |
| collection | DOAJ |
| description | Humanized mouse models can well be modified to study specific aspects of Graft-versus-Host Disease (GvHD). This paper shows the results of both macrophage depletion and (early) B-cell depletion in a humanized mouse model using RAG2-/-γc-/- mice injected with HuPBMCs. Macrophage depletion showed a significant decrease in survival and also lead to a change in the histomorphology of the xenogeneic reaction. Higher levels of infiltrating B-cells were observed in various organs of mice depleted for macrophages. With (early) B-cell depletion using Rituximab, a clear improvement on clinical symptoms was observed, even when probably only inactivated B-cells were deleted. However, the histological examinations only showed a significant morphological effect on liver fibrosis. This may be related to a difference in the mRNA levels of TGF-β. Also, lower mRNA levels of Tregs in some organs were observed after Rituximab treatment, which contradicts that a higher number of Tregs would always be related to less severe GvHD. Our data show that both macrophage depletion and (early) B-cell depletion in a xenogeneic mouse model can influence the clinical, histological, and cytokine production of a GvHD response. |
| format | Article |
| id | doaj-art-07f2728a6230461bacc463a61e5219f2 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-07f2728a6230461bacc463a61e5219f22025-02-03T06:13:13ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/35389633538963Modifying Graft-versus-Host Disease in a Humanized Mouse Model by Targeting Macrophages or B-CellsMarieke C. H. Hogenes0Suzanne van Dorp1Joyce van Kuik2Filipa R. P. Monteiro3Natalie ter Hoeve4Liane Guedes5Marijke R. van Dijk6Anton C. Martens7Roel A. de Weger8Laboratory for Pathology East Netherlands, (LABPON), P.O. Box 510, 7550 AM Hengelo, NetherlandsDepartment of Hematology (DIGD) UMC Utrecht, Utrecht, NetherlandsDepartment of Pathology UMC Utrecht, Utrecht, NetherlandsDepartment of Pathology UMC Utrecht, Utrecht, NetherlandsDepartment of Pathology UMC Utrecht, Utrecht, NetherlandsDepartment of Pathology UMC Utrecht, Utrecht, NetherlandsDepartment of Pathology UMC Utrecht, Utrecht, NetherlandsDepartment of Hematology, VU University Medical Centre, Amsterdam, NetherlandsDepartment of Pathology UMC Utrecht, Utrecht, NetherlandsHumanized mouse models can well be modified to study specific aspects of Graft-versus-Host Disease (GvHD). This paper shows the results of both macrophage depletion and (early) B-cell depletion in a humanized mouse model using RAG2-/-γc-/- mice injected with HuPBMCs. Macrophage depletion showed a significant decrease in survival and also lead to a change in the histomorphology of the xenogeneic reaction. Higher levels of infiltrating B-cells were observed in various organs of mice depleted for macrophages. With (early) B-cell depletion using Rituximab, a clear improvement on clinical symptoms was observed, even when probably only inactivated B-cells were deleted. However, the histological examinations only showed a significant morphological effect on liver fibrosis. This may be related to a difference in the mRNA levels of TGF-β. Also, lower mRNA levels of Tregs in some organs were observed after Rituximab treatment, which contradicts that a higher number of Tregs would always be related to less severe GvHD. Our data show that both macrophage depletion and (early) B-cell depletion in a xenogeneic mouse model can influence the clinical, histological, and cytokine production of a GvHD response.http://dx.doi.org/10.1155/2019/3538963 |
| spellingShingle | Marieke C. H. Hogenes Suzanne van Dorp Joyce van Kuik Filipa R. P. Monteiro Natalie ter Hoeve Liane Guedes Marijke R. van Dijk Anton C. Martens Roel A. de Weger Modifying Graft-versus-Host Disease in a Humanized Mouse Model by Targeting Macrophages or B-Cells Journal of Immunology Research |
| title | Modifying Graft-versus-Host Disease in a Humanized Mouse Model by Targeting Macrophages or B-Cells |
| title_full | Modifying Graft-versus-Host Disease in a Humanized Mouse Model by Targeting Macrophages or B-Cells |
| title_fullStr | Modifying Graft-versus-Host Disease in a Humanized Mouse Model by Targeting Macrophages or B-Cells |
| title_full_unstemmed | Modifying Graft-versus-Host Disease in a Humanized Mouse Model by Targeting Macrophages or B-Cells |
| title_short | Modifying Graft-versus-Host Disease in a Humanized Mouse Model by Targeting Macrophages or B-Cells |
| title_sort | modifying graft versus host disease in a humanized mouse model by targeting macrophages or b cells |
| url | http://dx.doi.org/10.1155/2019/3538963 |
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