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Abstract: FR-PO1119

T Cell-Specific miR-17-92 Knockout Improved Skin Graft Tolerance by Modulating T Follicular Helper Cell Development and Regulatory T Cell Activity

Session Information

  • Transplantation: Basic
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

  • 1901 Transplantation: Basic

Author

  • Yang, Huang-Yu, Chang Gung Memorial Hospital, Taoyuan, Taiwan
Background

T follicular helper (TFH) cell provide crucial growth signals to germinal center (GC) B cells supporting antibody production.Tight control of TFH numbers maintains self-tolerance. Regulatory T (Treg) cells play a critical role in maintaining self-tolerance and controlling the magnitude of physiologic immune response. The Treg transcription factor forkhead box P3 (Foxp3) works in concert with other co-regulator molecules to determine suppressive phenotype of Treg. MicroRNA-17-92 (MiR-17-92) has been shown in our previous study to regulate the suppressive effect of Treg on mice EAE models. The knockout of Mir-17-92 increase the immunosuppressive activity of Treg.

Methods

We generated T cell specific miR-17-92 knockout (miR-17-92-/-) mice, followed by skin transplantation. B6 miR-17-92 -/- and B6 wild type littermates were used as recipients of BALB/c skin grafts. By bioinformatics study, possible targets of mir-17-92, related to Treg function was evaluated. In addition, we performed a MLR (mixed lymphoid reaction) by co-culture donor APC with recipient derived T cells.

Results

The sirolimus-treated, miR-17-92 -/- mice showed less TFH cells, less GC B cells and the less plasma cells as compared with those in the sirolimus-treated, wild type mice. Consistent with the reduction germinal center response, skin histological analysis revealed a lower mean histopathology score. Moreover, miR17-92 knockout enhance the suppression function of Tregs. Th1 and Th17 are decreased in the miR-17-92 -/- mice. Moreover, T cells from miR-17-92 -/- mice demonstrated a donor antigen-specific hypo-responsiveness in vitro MLR.

Conclusion

We found that the skin graft survival was significantly better in the sirolimus-treated, miR-17-92 -/- mice, unveiling the future therapeutic potential of microRNA manipulation in transplantation.

Funding

  • Government Support - Non-U.S.