title: Effect of upregulated TLR2 expression from G-CSF-mobilized donor grafts on acute graft-versus-host disease.
abstract: Our previous study demonstrated that G-CSF treatment increased the expression of TLR2 in donor grafts; this contributed to rapid engraftment after allogeneic hematopoietic stem cell transplantation (HSCT) in mice. In the current study, we investigated the effects of upregulated TLR2 expression in G-CSF-mobilized donor grafts on acute graft-versus-host disease (GVHD). We found that TLR2 was highly expressed on myeloid cell populations but not T and B cells from the spleens of G-CSF-treated donor mice. After transplantation, the mortality and disease severity in recipients were not significantly different between G-CSF-treated TLR2-/- and wt donor grafts. Although endogenous TLR2 ligand was detected in the serum of both recipients, T cells from TLR2-/- and wt donors have the same ability regarding alloreactivity. Moreover, the blockade of TLR2 signaling in recipients by administering anti-TLR2 blocking antibody after BMT did not lead to a significant difference in acute GVHD compared with control IgG treatment. However, the hematopoietic ability of G-CSF-mobilized lin−c-kit+ HSCs from TLR2-/- donor grafts was lower than that from wt donor grafts. Our results demonstrate that upregulated TLR2 expression in G-CSF-mobilized donor grafts has no effect on acute GVHD, suggesting that TLR2 is a valuable target for increasing HSCT efficiency in order to enhance engraftment without exacerbating acute GVHD.
authors.affiliation: Department of Hemato/Oncology, Busan Paik Hospital, College of Medicine, Inje University, Busan 614-735, South Korea.
authors.forename: Won-Sik
authors.initials: WS
authors.lastname: Lee
authors.affiliation: Department of Orthopedic Surgery, Busan Paik Hospital, College of Medicine, Inje University, Busan 614-735, South Korea.
authors.forename: Joo-Yong
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Inje University, Busan 614-735, South Korea.
authors.forename: Hae-Jeong
authors.initials: HJ
authors.lastname: Won
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Inje University, Busan 614-735, South Korea.
authors.forename: Soung-Min
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Inje University, Busan 614-735, South Korea.
authors.forename: Young-Sill
authors.initials: YS
authors.lastname: Suh
authors.affiliation: Department of Hemato/Oncology, Haeundae Paik Hospital, College of Medicine, Inje University, Busan 612-030, South Korea.
authors.forename: Young-Don
authors.initials: YD
authors.lastname: Joo
authors.affiliation: Department of Hemato/Oncology, Busan Paik Hospital, College of Medicine, Inje University, Busan 614-735, South Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Medicine, Inje University, Busan 614-735, South Korea.
authors.forename: Won-Hee
authors.initials: WH
authors.lastname: Jang
authors.affiliation: Department of Nephrology, Busan Paik Hospital, College of Medicine, Inje University, Busan 614-735, South Korea.
authors.forename: Sun-Woo
authors.initials: SW
authors.lastname: Kang
authors.affiliation: Department of Pathology, College of Medicine, Inje University, Busan 614-735, South Korea.
authors.forename: Mi-Sun
authors.initials: MS
authors.lastname: Kang
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Inje University, Busan 614-735, South Korea.
authors.forename: Sae-Gwang
authors.initials: SG
authors.lastname: Park
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Inje University, Busan 614-735, South Korea.
authors.forename: Il-Whan
authors.initials: IW
authors.lastname: Choi
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Inje University, Busan 614-735, South Korea.
authors.forename: Inhak
authors.initials: I
authors.lastname: Choi
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Inje University, Busan 614-735, South Korea. Electronic address: sseo@inje.ac.kr.
authors.forename: Su-Kil
authors.initials: SK
authors.lastname: Seo
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000187:drug effects / Q000378:metabolism; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D016179:Granulocyte Colony-Stimulating Factor
keywords: GVHD; Peripheral blood stem cell transplantation; TLR2