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


RESULTS
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.


CONCLUSIONS
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.
Christiane
C
Broichhausen
Paloma
P
Riquelme
Edward K
EK
Geissler
James A
JA
Hutchinson
D064987:Cell- and Tissue-Based Therapy; D006084:Graft Rejection / Q000276:immunology / Q000628:therapy; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000637:transplantation; D016377:Organ Transplantation; D015427:Reperfusion Injury / Q000276:immunology / Q000503:physiopathology; D023001:Transplantation Tolerance / Q000276:immunology*