TY - JOUR
T1 - Modifying graft-versus-host disease in a humanized mouse model by targeting macrophages or b-cells
AU - Hogenes, Marieke C.H.
AU - Van Dorp, Suzanne
AU - Van Kuik, Joyce
AU - Monteiro, Filipa R.P.
AU - Ter Hoeve, Natalie
AU - Guedes, Liane
AU - Van Dijk, Marijke R.
AU - Martens, Anton C.
AU - De Weger, Roel A.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
KW - Animals
KW - B-Lymphocytes/immunology
KW - Disease Models, Animal
KW - Female
KW - Graft vs Host Disease/immunology
KW - Hematopoietic Stem Cell Transplantation
KW - Humans
KW - Leukocytes, Mononuclear/immunology
KW - Liver Cirrhosis/immunology
KW - Lymphocyte Depletion
KW - Macrophages/immunology
KW - Mice
KW - Mice, SCID
KW - T-Lymphocytes, Regulatory/immunology
UR - http://www.scopus.com/inward/record.url?scp=85068215747&partnerID=8YFLogxK
U2 - 10.1155/2019/3538963
DO - 10.1155/2019/3538963
M3 - Article
C2 - 31205954
AN - SCOPUS:85068215747
SN - 2314-8861
VL - 2019
JO - Journal of Immunology Research
JF - Journal of Immunology Research
M1 - 3538963
ER -