Tolerance induced by IL-6 deficient donor heart is significantly involved in myeloid-derived suppressor cells (MDSCs)

• Transplant tolerance induced by IL-6 deficient donor is supported by regulatory T cells.
• Utilization of IL-6 deficient heart grafts could cause a significant prolongation of allograft survival.
• MDSCs rather than Th17 cells are closely involved in induced tolerance by IL-6 deficient donor heart.

ObjectivesTransplant tolerance induced by IL-6 deficient donor is supported by regulatory T cells (Tregs). However, it is unknown whether innate immunoregulatory cells such as myeloid-derived suppressor cells (MDSCs) are involved in the process.Materials and methodsIn this study, we demonstrate the role of MDSCs by transplanting IL-6 deficient heart grafts into wild-type recipients in a murine allogeneic transplant model.ResultsOur data further revealed that utilization of IL-6 deficient heart grafts could cause a significant prolongation of allograft survival (Mantel–Cox Test, p = 0.001; Gehan–Breslow–Wilcoxon Test, p = 0.0016) and a remarkable increase of the frequency of CD11b + Gr1− low in the recipients' spleens (p = 0.0028).ConclusionsMDSCs rather than Th17 cells are closely involved in induced tolerance by IL-6 deficient donor heart. This unveiled mechanism of targeting IL-6 or its signaling pathway may provide a novel insight into preventing allograft rejection for non-sensitized transplant recipients.