The divergent roles of macrophages in solid organ transplantation

Abstract

Purpose of review: This review summarizes the phenotype and function of macrophages in the context of solid organ transplantation and will focus on fundamental insights into their paradoxical pro-inflammatory versus suppressive function. We will also discuss the therapeutic potential of regulatory macrophages in tolerance induction.

Recent findings: Macrophages are emerging as an essential element of solid organ transplantation. Macrophages are involved in the pathogenesis of ischemia reperfusion injury, as well as both acute and chronic rejection, exacerbating injury through secretion of inflammatory effectors and by amplifying adaptive immune responses. Notably, not all responses associated with macrophages are deleterious to the graft, and graft protection can in fact be conferred by macrophages. This has been attributed to the presence of macrophages with tissue-repair capabilities, as well as the effects of regulatory macrophages.

Summary: The explosion of new information on the role of macrophages in solid organ transplantation has opened up new avenues of research and the possibility of therapeutic intervention. However, the role of myeloid cells in graft rejection, resolution of rejection and tissue repair remains poorly understood. A better understanding of plasticity and regulation of monocyte polarization is vital for the development of new therapies for the treatment of acute and chronic transplant rejection.

Figure 1. Macrophage plasticity and function in the context of allograft rejection

a) M1 macrophages are classically activated, damage graft endothelium, recruit additional leukocytes, and mediate tissue injury. They are the dominant phenotype in acute rejection and their activity can be modulated by blockade of their activation or the factors they produce. b) M2 macrophages are alternatively activated, mediate tissue repair and injury resolution, and promote fibrosis. This subset is predominantly found in chronically-damaged allografts. c) Mregs are activated in a fashion distinct from the other two subsets. They modulate anti-inflammatory response, have T cell suppressive capacity, and are being investigated for use in cell-based therapy.