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Regulatory macrophages as therapeutic targets and therapeutic agents in solid organ transplantation

Broichhausen, Christiane; Riquelme, Paloma; Geissler, Edward K.; Hutchinson, James A.

Current Opinion in Organ Transplantation: August 2012 - Volume 17 - Issue 4 - p 332–342
doi: 10.1097/MOT.0b013e328355a979
TOLERANCE INDUCTION: Edited by Fred Fändrich
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Purpose of review This review aims to provide a basic introduction to human macrophage biology and an appreciation of the diverse roles played by macrophage subsets in allograft damage and repair. Current and future strategies for therapeutically manipulating macrophage behaviour are discussed.

Recent findings Macrophages are extremely versatile effector cells that exert both immunostimulatory and immunosuppressive effects. This adaptability cannot be explained by differentiation into committed sublineages, but instead reflects the ability of macrophages to rapidly transition between states of functional polarisation. Consequently, categorisation of macrophage subpopulations is not straightforward and this, in turn, creates difficulties in studying their pathophysiology. Nevertheless, particular macrophage subpopulations have been implicated in exacerbating or attenuating ischaemia-reperfusion injury, rejection reactions and allograft fibrosis. Three general strategies for therapeutically targeting macrophages can be envisaged, namely, depletional approaches, in-situ repolarisation towards a regulatory or tissue-reparative phenotype, and ex-vivo generation of regulatory macrophages (M reg) as a cell-based therapy.

Summary As critical determinants of the local and systemic immune response to solid organ allografts, macrophage subpopulations represent attractive therapeutic targets. Rapid progress is being made in the implementation of novel macrophage-targeted therapies, particularly in the use of ex-vivo-generated M regs as a cell-based medicinal product.

Department of Surgery and Regensburg Center for Interventional Immunology, University Hospital Regensburg, University of Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg, Germany

Correspondence to Dr James A. Hutchinson, Department of Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg 93053, Germany. Tel: +49 941 944 6831; fax: +49 941 944 6772; e-mail: james.hutchinson@klinik.uni-regensburg.de

© 2012 Lippincott Williams & Wilkins, Inc.