Modifying graft-versus-host disease in a humanized mouse model by targeting macrophages or b-cells

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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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.

Original languageEnglish
Article number3538963
Number of pages15
JournalJournal of Immunology Research
Volume2019
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • Animals
  • B-Lymphocytes/immunology
  • Disease Models, Animal
  • Female
  • Graft vs Host Disease/immunology
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Leukocytes, Mononuclear/immunology
  • Liver Cirrhosis/immunology
  • Lymphocyte Depletion
  • Macrophages/immunology
  • Mice
  • Mice, SCID
  • T-Lymphocytes, Regulatory/immunology

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