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

TY - JOUR

T1 - Absence of P-selectin in recipients of allogeneic bone marrow transplantation ameliorates experimental graft-versus-host disease

AU - Lu, Sydney X.

AU - Holland, Amanda M.

AU - Na, Il Kang

AU - Terwey, Theis H.

AU - Alpdogan, Onder

AU - Bautista, Jhoanne L.

AU - Smith, Odette M.

AU - Suh, David

AU - King, Christopher

AU - Kochman, Adam

AU - Hubbard, Vanessa M.

AU - Rao, Uttam K.

AU - Yim, Nury

AU - Liu, Chen

AU - Laga, Alvaro C.

AU - Murphy, George

AU - Jenq, Robert R.

AU - Zakrzewski, Johannes L.

AU - Penack, Olaf

AU - Dykstra, Lindsay

AU - Bampoe, Kevin

AU - Perez, Lia

AU - Furie, Bruce

AU - Furie, Barbara

AU - Van Den Brink, Marcel R.M.

PY - 2010/8/1

Y1 - 2010/8/1

N2 - 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 in-filtration 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.

AB - 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 in-filtration 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.

UR - https://www.scopus.com/pages/publications/77956402670

U2 - 10.4049/jimmunol.0903148

DO - 10.4049/jimmunol.0903148

M3 - Article

C2 - 20622117

SN - 0022-1767

VL - 185

SP - 1912

EP - 1919

JO - Journal of Immunology

JF - Journal of Immunology

IS - 3

ER -