2024-03-29T02:04:29Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/85452022-09-29T11:54:24Zcom_20.500.12105_2060com_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_2061
00925njm 22002777a 4500
dc
Hashimoto, Daigo
author
Chow, Andrew
author
Greter, Melanie
author
Saenger, Yvonne
author
Kwan, Wing-Hong
author
Leboeuf, Marylene
author
Ginhoux, Florent
author
Ochando, Jordi
author
Kunisaki, Yuya
author
van Rooijen, Nico
author
Liu, Chen
author
Teshima, Takanori
author
Heeger, Peter S
author
Stanley, E Richard
author
Frenette, Paul S
author
Merad, Miriam
author
2011-05-09
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.
J Exp Med. 2011 May 9;208(5):1069-82. doi: 10.1084/jem.20101709. Epub 2011 May 2.
0022-1007
http://hdl.handle.net/20.500.12105/8545
21536742
10.1084/jem.20101709
1540-9538
The Journal of experimental medicine
Pretransplant CSF-1 therapy expands recipient macrophages and ameliorates GVHD after allogeneic hematopoietic cell transplantation