Modifying Graft-versus-Host Disease in a Humanized Mouse Model by Targeting Macrophages or B-Cells

Autor: 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
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Journal of Immunology Research, Vol 2019 (2019)
Druh dokumentu: article
ISSN: 2314-8861
2314-7156
DOI: 10.1155/2019/3538963
Popis: 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.
Databáze: Directory of Open Access Journals
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