Targeting Macrophages in Organ Transplantation: A Step Toward Personalized Medicine

Mar 12, 2024Transplantation

Using Immune Cells to Improve Organ Transplants for Personalized Treatment

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Macrophages play a critical role in both allograft rejection and tolerance in organ transplantation.

Allograft rejection involves complex interactions between innate and adaptive immune cells.
Macrophages contribute to ischemia-reperfusion injury and both acute and chronic rejection of transplanted organs.
These cells exhibit a phenomenon known as 'trained immunity,' enhancing their inflammatory responses upon subsequent exposures.
Macrophages can also adopt immunoregulatory roles, which may facilitate allograft tolerance.
Understanding macrophage plasticity and polarization is essential for developing targeted therapies in transplantation.

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Organ transplantation remains the most optimal strategy for patients with end-stage organ failure. However, prevailing methods of immunosuppression are marred by adverse side effects, and allograft rejection remains common. It is imperative to identify and comprehensively characterize the cell types involved in allograft rejection, and develop therapies with greater specificity. There is increasing recognition that processes mediating allograft rejection are the result of interactions between innate and adaptive immune cells. Macrophages are heterogeneous innate immune cells with diverse functions that contribute to ischemia-reperfusion injury, acute rejection, and chronic rejection. Macrophages are inflammatory cells capable of innate allorecognition that strengthen their responses to secondary exposures over time via "trained immunity." However, macrophages also adopt immunoregulatory phenotypes and may promote allograft tolerance. In this review, we discuss the roles of macrophages in rejection and tolerance, and detail how macrophage plasticity and polarization influence transplantation outcomes. A comprehensive understanding of macrophages in transplant will guide future personalized approaches to therapies aimed at facilitating tolerance or mitigating the rejection process.

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Targeting Macrophages in Organ Transplantation: A Step Toward Personalized Medicine

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