Absence of P-selectin in recipients of allogeneic bone marrow transplantation ameliorates experimental graft-versus-host disease

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Item Type:	Article
Title:	Absence of P-selectin in recipients of allogeneic bone marrow transplantation ameliorates experimental graft-versus-host disease
Creators Name:	Lu, S.X., Holland, A.M., Na, I.K., Terwey, T.H., Alpdogan, O., Bautista, J.L., Smith, O.M., Suh, D., King, C., Kochman, A., Hubbard, V.M., Rao, U.K., Yim, N., Liu, C., Laga, A.C., Murphy, G., Jenq, R.R., Zakrzewski, J.L., Penack, O., Dykstra, L., Bampoe, K., Perez, L., Furie, B., Furie, B. and van den Brink, M.R.M.
Abstract:	Alloreactive T cells are crucial for graft-versus-host disease (GVHD) pathophysiology, and modulating their trafficking patterns has been efficacious in ameliorating experimental disease. We report in this paper that P-selectin, a glycoprotein found on resting and inflamed endothelium, is important for donor alloreactive T cells trafficking into GVHD target organs, such as the intestines and skin. Compared with wild-type (WT) recipients of allogeneic bone marrow transplantation, P-selectin(-/-) recipients exhibit decreased GVHD mortality and decreased GVHD of the skin, liver, and small bowels. This was associated with diminished infiltration of alloactivated T cells into the Peyer's patches and small bowels, coupled with increased numbers of donor T cells in the spleen and secondary lymphoid organs (SLOs). Surprisingly, however, donor T cells deficient for P-selectin glycoprotein ligand 1, the most well described P-selectin ligand, mediated GVHD similar to WT T cells and accumulated in SLO and target organs in similar numbers as WT T cells. This suggests that P-selectin may be required for trafficking into inflamed tissues but not SLO and that donor T cells may use multiple P-selectin ligands apart from P-selectin glycoprotein ligand 1 to interact with P-selectin and traffic into inflamed tissues during GVHD. We conclude that targeting P-selectin may be a viable strategy for GVHD prophylaxis or treatment.
Keywords:	Animal Disease Models, Bone Marrow Transplantation, Graft vs Host Disease, Homologous Transplantation, Inflammation Mediators, Ligands, Lymphocyte Activation, Membrane Glycoproteins, P-Selectin, T-Lymphocyte Subsets, Vascular Endothelium, Animals, Mice
Source:	Journal of Immunology
ISSN:	0022-1767
Publisher:	American Association of Immunologists
Volume:	185
Number:	3
Page Range:	1912-1919
Date:	1 August 2010
Official Publication:	https://doi.org/10.4049/jimmunol.0903148
PubMed:	View item in PubMed

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