Donor-derived exosomes induce specific regulatory T cells to suppress immune inflammation in the allograft heart

Abstract

To inhibit the immune inflammation in the allografts can be beneficial to organ transplantation. This study aims to induce the donor antigen specific regulatory T cells (Treg cell) inhibit the immune inflammation in the allograft heart. In this study, peripheral exosomes were purified from the mouse serum. A heart transplantation mouse model was developed. The immune inflammation of the allograft heart was assessed by histology and flow cytometry. The results showed that the donor antigen-specific T helper (Th)2 pattern inflammation was observed in the allograft hearts; the inflammation was inhibited by immunizing the recipient mice with the donor-derived exosomes. Purified peripheral exosomes contained integrin MMP1a; the latter induced CD4+ T cells to express Fork head protein-3 and transforming growth factor (TGF)-β via inhibiting the Th2 transcription factor, GATA binding protein 3, in CD4+ T cells. Administration with the donor-derived exosomes significantly prolonged the allograft heart survival. We conclude that the donor-derived peripheral exosomes have the capacity to inhibit the immune inflammation in the allograft heart via inducing specific Treg cells, implicating that administration with the donor-derived exosomes may be beneficial to cardiac transplantation.

In vivo reprogramming of immune cells: Technologies for induction of antigen-specific tolerance

“…Exosomes derived from PBMCs have been used to prolong cardiac transplants in a C57BL/6 to BALB/c model [105]. Song et al could extend cardiac allografts 40 days using 2 doses of exosomes from donor C57BL/6 mice.…”

Tolerogenic dendritic cells in organ transplantation

“…In the case of DCs and other professional APCs, this may include MHC molecules, T‐cell CM, as well as adhesion molecules, indicating that DC‐derived exosomes function as Ag‐presenting nanovesicles (<100 nm) . While it is becoming clear that DC‐derived exosomes bearing MHC molecules are effective intercellular communicators and provide activating signals that promote anti‐donor immune responses , donor‐derived exosomes also participate in the induction and maintenance of peripheral T‐cell tolerance .…”

The multifaceted role of extracellular vesicles in metastasis: Priming the soil for seeding

“…In vitro and in vivo assays demonstrated that exosomes released by innate immune cells, stromal cells and adaptive immune cells are critical during inflammation by expanding the pro‐inflammatory response, activating other immune cells . Additionally, they have an important role in the progression of the inflammatory response to resolution, immune tolerance and immunomodulation . In summary, exosomes have a critical role in amplifying the signal emitted by the source cells in the immune response.…”

“…Exosomes have an important role in the physiopathological immune response. In vitro and in vivo assays demonstrated that exosomes released by innate immune cells, 75-80 stromal cells 81,82 and adaptive immune cells [83][84][85] are critical during inflammation by expanding the pro-inflammatory response, activating other immune cells. 75,76,78,80,82,85 Additionally, they have an important role in the progression of the inflammatory response to resolution, 78 immune tolerance 77,79 and immunomodulation.…”

“…75,76,78,80,82,85 Additionally, they have an important role in the progression of the inflammatory response to resolution, 78 immune tolerance 77,79 and immunomodulation. 83,84 In summary, exosomes have a critical role in amplifying the signal emitted by the source cells in the immune response. The final effect will also depend on individual target cells.…”