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.
MMP1a plays a critical role in the donor-derived exosome-induced allograft tolerance
The recipient mice of heart allograft were treated with the exosomes (or non-donor-derived exosomes; #) and anti-MMP1a (0.25 mg/mouse) or MMP1a (0.1 mg/mouse) on the day of surgery. (A) the heart histology image shows infiltration of inflammatory cells. (B–D) the histograms show the frequency of IL-4+ T cells (B), IFN-γ+ T cells and proliferating CD4+ T cells (D). Each group consists of 12 mice. Samples from 4 mice were pooled as one sample.