Macrophages as Effectors of Acute and Chronic Allograft Injury

Abstract

Organ transplants give a second chance of life to patients with end-stage organ failure. However, the immuno-logical barriers prove to be very challenging to overcome and graft rejection remains a major hurdle to long-term transplant survival. For decades, adaptive immunity has been the focus of studies, primarily based on the belief that T cells are necessary and sufficient for rejection. With better-developed immunosuppressive drugs and protocols that effectively control adaptive cells, innate immune cells have emerged as key effector cells in triggering graft injury and have therefore attracted much recent attention. In this review, we discuss current understanding of macrophages and their role in transplant rejection, their dynamics, distinct phenotypes, locations, and functions. We also discuss novel therapeutic approaches under development to target macrophages in transplant recipients.

Keywords: Chronic rejection; Inflammation; Innate immunity; Macrophages; Rejection; Transplantation.

Fig. 1

Macrophages can be polarized into different subsets with distinct functional attributes. M1 cells are induced by TLR ligands and Th1 cytokines, and exhibit potent pro-inflammatory features; M2 cells develop in the presence of IL-4 and IL-13 (Th2 cytokines), and express regenerative and pro-fibrotic activities. Some M2 cells can be immunosuppressive