Nanoparticle-Based Modulation and Monitoring of Antigen-Presenting Cells in Organ Transplantation.

Jordi Ochando,Mounia S Braza

doi:10.3389/fimmu.2017.01888

Jordi Ochando, Mounia S Braza

Open Access

https://doi.org/10.3389/fimmu.2017.01888

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Abstract

Donor-specific unresponsiveness while preserving an intact immune function remains difficult to achieve in organ transplantation. Induction of tolerance requires a fine modulation of the interconnected innate and adaptive immune systems. Antigen-presenting cells (APCs) predominate during allograft rejection and create a highly inflammatory context where allospecific T cells are primed. Currently, the available protocols to prevent allograft rejection include a cocktail of drugs that are efficient in the short-term, but with severe long-term side effects and considerable toxicity. Consequently, better and less burdensome strategies are needed to promote indefinite allograft survival. Targeted delivery of immunosuppressive drugs that prevent the alloimmune response may address some of these problems. Nanoparticle-based approaches represent a promising strategy to negatively modulate the alloresponse by specifically delivering small compounds to APCs in vivo. Nanoparticles are also used as integrating imaging moieties to monitor inflammation for diagnostic purposes. Therefore, nanotechnology approaches represent an attractive strategy to deliver and monitor the efficacy of immunosuppressive therapy in organ transplantation with the potential to improve the clinical treatment of transplant patients.

Highlights

Transplantation is a life-enhancing therapeutic option for tens of thousands of patients with end-stage organ failure
We introduce the synthetic high-density lipoprotein (HDL) nanoparticles (HDL-NPs), which represent an emerging and very promising nanotherapeutic option to be exploited in organ transplantation
While monocyte-derived cell accumulation in transplanted organs has long been recognized as a feature of allograft rejection [13], recent data suggest that monocyte-derived macrophages inhibit graft-reactive immune responses [14] and mediate the induction of transplantation tolerance [10]

Summary

INTRODUCTION

Transplantation is a life-enhancing therapeutic option for tens of thousands of patients with end-stage organ failure. Novel therapeutic approaches that target the adaptive immune response have been developed, but the long-term transplant outcomes remain suboptimal This underlines the need for additional approaches to develop tolerance-inducing protocols. Therapeutic approaches that target myeloid cells in vivo and deliver immunomodulatory agents that prevent activation of the adaptive immune response represents a largely unexplored approach to promote indefinite allograft survival. In this mini review, we first discuss the current state and perspectives of nanotherapy in transplantation by focusing on nanoparticles, for modulation and immunosuppressive drug delivery to antigen-presenting cells (APCs). We raise several outstanding questions about the use of nanoparticles in organ transplantation to conclude that this technology represents an additional therapeutic option to prevent transplant rejection and promote organ acceptance

APCs AS A THERAPEUTIC TARGET FOR IMMUNOSUPPRESSIVE THERAPY IN TRANSPLANTATION

CONCLUDING REMARKS AND OUTSTANDING QUESTIONS