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oai:repisalud.isciii.es:20.500.12105/85452024-09-27T23:41:45Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

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. 10.1084/jem.20101709 1540-9538 0022-1007 The Journal of experimental medicine 21536742 http://hdl.handle.net/20.500.12105/8545 Pretransplant CSF-1 therapy expands recipient macrophages and ameliorates GVHD after allogeneic hematopoietic cell transplantation