Apoptotic cell-based therapies against transplant rejection: role of recipient’s dendritic cells |
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Authors: | Adrian E Morelli Adriana T Larregina |
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Institution: | (1) T.E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, E1546 Biomedical Science Tower, 200 Lothrop St., Pittsburgh, PA 15213-2582, USA;(2) Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA;(3) Department of Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA;(4) Department of Dermatology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA |
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Abstract: | One of the ultimate goals in transplantation is to develop novel therapeutic methods for induction of donor-specific tolerance
to reduce the side effects caused by the generalized immunosuppression associated to the currently used pharmacologic regimens.
Interaction or phagocytosis of cells in early apoptosis exerts potent anti-inflammatory and immunosuppressive effects on antigen
(Ag)-presenting cells (APC) like dendritic cells (DC) and macrophages. This observation led to the idea that apoptotic cell-based
therapies could be employed to deliver donor-Ag in combination with regulatory signals to recipient’s APC as therapeutic approach
to restrain the anti-donor response. This review describes the multiple mechanisms by which apoptotic cells down-modulate
the immuno-stimulatory and pro-inflammatory functions of DC and macrophages, and the role of the interaction between apoptotic
cells and APC in self-tolerance and in apoptotic cell-based therapies to prevent/treat allograft rejection and graft-versus-host
disease in murine experimental systems and in humans. It also explores the role that in vivo-generated apoptotic cells could
have in the beneficial effects of extracorporeal photopheresis, donor-specific transfusion, and tolerogenic DC-based therapies
in transplantation. |
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