Hsp70, a highly conserved protein, has been shown to induce strong immune responses and to reduce inflammation. However, its mechanism is not clear, especially in the field of transplantation. Using VER155008, a HSP70 inhibitor, we found that VER155008 could induce long-term allograft survival in the mouse heart transplantation model. Ex vivo analysis showed that more IL-10+ and Foxp3+ T cells were found in the graft infiltrating lymphocytes. In vitro, VER155008 could induce Treg differentiation, and VER155008 treated Treg could better inhibit T cell proliferation by co-culture with CD4+CD25- T cells. Moreover, VER155008 treated Treg could induce longer allograft survival in the mouse heart transplantation model. At last, we found Hsp70 could bind to mTOR and Rictor, but not raptor by co-IP experiment. And in vitro protein interaction experiment showed that mTORC2 from VER155008 treated T cells could not inhibit the Akt Ser473 phosphorylation. Our results showed that Hsp70 inhibitor could Treg through mTORC2/Akt pathway, and induce transplant tolerance.

CITATION INFORMATION: Gu G., Lu T., Xu N., Xia Q. Hsp70 Inhibitor Could Induce Transplant Tolerance through mTORC2/Akt Pathway Am J Transplant. 2017;17 (suppl 3).

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