Regulatory T Cell-Derived Exosomes: Possible Therapeutic and Diagnostic Tools in Transplantation

Abstract

Exosomes are extracellular vesicles released by many cells of the body. These small vesicles play an important part in intercellular communication both in the local environment and systemically, facilitating in the transfer of proteins, cytokines as well as miRNA between cells. The observation that exosomes isolated from immune cells such as dendritic cells (DCs) modulate the immune response has paved the way for these structures to be considered as potential immunotherapeutic reagents. Indeed, clinical trials using DC derived exosomes to facilitate immune responses to specific cancer antigens are now underway. Exosomes can also have a negative effect on the immune response and exosomes isolated from regulatory T cells (Tregs) and other subsets of T cells have been shown to have immune suppressive capacities. Here, we review what is currently known about Treg derived exosomes and their contribution to immune regulation, as well as highlighting their possible therapeutic potential for preventing graft rejection, and use as diagnostic tools to assess transplant outcome.

Advances in the immunology of heart transplantation

“…32 For instance, exosomes isolated from activated Tregs expanded ex vivo could be further modified to express specific inhibitory microRNAs, cytokines or surface molecules to be used in conjunction with adoptive Treg therapy to promote donor-specific unresponsiveness. 33 Although the field of exosome therapy is still in its infancy, it has real potential to benefit our transplant patients in time.…”

Cutting Edge: Regulation of Exosome Secretion by the Integral MAL Protein in T Cells

“…Exosomes from regulatory T cells can suppress effector T cells by delivering microRNAs via exosomes (4). These findings suggest that modulation of the exosome route in T cells may be of therapeutic value for preventing T cellmediated diseases such as inflammation or for interfering with the progression of HIV-1 infection (5,6).…”

Exosomes and tumor-mediated immune suppression

“…Despite emerging evidence that the immunostimulatory or immunoinhibitory functions of TEX depend on the type of cargo and the functional status of immune cells in the tumor microenvironment (TME) and thus might be highly variable, it has been difficult to reconcile these two aspects of TEX functionality. Interestingly, in fields other than cancer, including inflammation, autoimmunity, transplantation, and pregnancy, the immunosuppressive potential of exosomes is not only acknowledged, but is explored for the development of novel therapeutic strategies (18)(19)(20)(21)(22). Given the immunoinhibitory nature of the TME in humans, it is unlikely that TEX, which increase in numbers with disease stage and progression (1,8), are involved in boosting immune responses.…”