title: Dysfunction of bone marrow vascular niche in acute graft-versus-host disease after MHC-haploidentical bone marrow transplantation.
abstract: Acute graft-versus-host disease (aGvHD) is the most common complication of allogeneic hematopoietic stem cell transplantation (HSCT), which is often accompanied by impaired hematopoietic reconstitution. Sinusoidal endothelial cells (SECs) constitute bone marrow (BM) vascular niche that plays an important role in supporting self-renewal capacity and maintaining the stability of HSC pool. Here we provide evidences that vascular niche is a target of aGvHD in a major histocompatibility complex (MHC)-haploidentical matched murine HSCT model. The results demonstrated that hematopoietic cells derived from GvHD mice had the capacity to reconstitute hematopoiesis in healthy recipient mice. However, hematopoietic cells from healthy donor mice failed to reconstitute hematopoiesis in GvHD recipient mice, indicating that the BM niche was impaired by aGvHD in this model. We further demonstrated that SECs were markedly reduced in the BM of aGvHD mice. High level of Fas and caspase-3 expression and high rate of apoptosis were identified in SECs, indicating that SECs were destroyed by aGvHD in this murine HSCT model. Furthermore, high Fas ligand expression on engrafted donor CD4(+), but not CD8(+) T cells, and high level MHC-II but not MHC-I expression on SECs, suggested that SECs apoptosis was mediated by CD4(+) donor T cells through the Fas/FasL pathway.
authors.affiliation: Department of Hematology, Institute of Hematology, Changhai Hospital, Shanghai, China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Hematology, Institute of Hematology, Changhai Hospital, Shanghai, China.
authors.forename: Xianmin
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Hematology, Institute of Hematology, Changhai Hospital, Shanghai, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Department of Hematology, Institute of Hematology, Changhai Hospital, Shanghai, China.
authors.forename: Gusheng
authors.initials: G
authors.lastname: Tang
authors.affiliation: Department of Hematology, Institute of Hematology, Changhai Hospital, Shanghai, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Hematology, Institute of Hematology, Changhai Hospital, Shanghai, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Hematology, Institute of Hematology, Changhai Hospital, Shanghai, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000209:etiology* / Q000503:physiopathology*; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008285:Major Histocompatibility Complex / Q000235:genetics; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D014184:Transplantation, Homologous; D019014:fas Receptor / Q000378:metabolism
chemical_list: C491899:Fas protein, mouse; D019014:fas Receptor; D053148:Caspase 3