title: Pretransplant CSF-1 therapy expands recipient macrophages and ameliorates GVHD after allogeneic hematopoietic cell transplantation.
abstract: Acute graft-versus-host disease (GVHD) results from the attack of host tissues by donor allogeneic T cells and is the most serious limitation of allogeneic hematopoietic cell transplantation (allo-HCT). Host antigen-presenting cells are thought to control the priming of alloreactive T cells and the induction of acute GVHD after allo-HCT. However, whereas the role of host DC in GVHD has been established, the contribution of host macrophages to GVHD has not been clearly addressed. We show that, in contrast to DC, reducing of the host macrophage pool in recipient mice increased donor T cell expansion and aggravated GVHD mortality after allo-HCT. We also show that host macrophages that persist after allo-HCT engulf donor allogeneic T cells and inhibit their proliferation. Conversely, administration of the cytokine CSF-1 before transplant expanded the host macrophage pool, reduced donor T cell expansion, and improved GVHD morbidity and mortality after allo-HCT. This study establishes the unexpected key role of host macrophages in inhibiting GVHD and identifies CSF-1 as a potential prophylactic therapy to limit acute GVHD after allo-HCT in the clinic.
authors.affiliation: Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Daigo
authors.initials: D
authors.lastname: Hashimoto
authors.forename: Andrew
authors.initials: A
authors.lastname: Chow
authors.forename: Melanie
authors.initials: M
authors.lastname: Greter
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Saenger
authors.forename: Wing-Hong
authors.initials: WH
authors.lastname: Kwan
authors.forename: Marylene
authors.initials: M
authors.lastname: Leboeuf
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
authors.forename: Jordi C
authors.initials: JC
authors.lastname: Ochando
authors.forename: Yuya
authors.initials: Y
authors.lastname: Kunisaki
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Takanori
authors.initials: T
authors.lastname: Teshima
authors.forename: Peter S
authors.initials: PS
authors.lastname: Heeger
authors.forename: E Richard
authors.initials: ER
authors.lastname: Stanley
authors.forename: Paul S
authors.initials: PS
authors.lastname: Frenette
authors.forename: Miriam
authors.initials: M
authors.lastname: Merad
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014184:Transplantation, Homologous
chemical_list: D016173:Macrophage Colony-Stimulating Factor