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Delayed allogeneic skin graft rejection in CD26-deficient mice

Authors

  • X. Zhao
  • K. Zhang
  • P. Daniel
  • N. Wisbrun
  • H. Fuchs
  • H. Fan

Journal

  • Cellular and Molecular Immunology

Citation

  • Cell Mol Immunol 16 (6): 557-567

Abstract

  • Organ transplantation is an effective therapeutic tool for treating many terminal diseases. However, one of the biggest challenges of transplantation is determining how to achieve the long-term survival of the allogeneic or xenogeneic transplant by, for example, preventing transplant rejection. In the current study, CD26 gene-knockout mice were used to investigate the potential role of CD26/dipeptidyl peptidase-4 (DPPIV) in allogeneic skin graft rejection by tail-skin transplantation. Compared with wild-type (CD26(+/+)) counterparts, CD26(–/–) mice showed reduced necrosis of grafts and delayed graft rejection after skin transplantation. Concentrations of serum IgG, including its subclasses IgG1 and IgG2a, were significantly reduced in CD26(–/–) mice during graft rejection. Moreover, after allogeneic skin transplantation, the secretion levels of the cytokines IFN-γ, IL-2, IL-6, IL-4, and IL-13 were significantly reduced, whereas the level of the cytokine IL-10 was increased in the serum of CD26(–/–) mice compared with that in the serum of CD26(+/+) mice. Additionally, the concentration of IL-17 in serum and the percentage of cells secreting IL-17 in mouse peripheral blood lymphocytes (MPBLs) were both significantly lower, while the percentage of regulatory T cells (Tregs) was significantly higher in MPBLs of CD26(–/–) mice than in those of CD26(+/+) mice. Furthermore, a lower percentage of CD8(+) T cells in MPBLs and fewer infiltrated macrophages and T cells in graft tissues of CD26(–/–) mice were detected during graft rejection. These results indicate that CD26 is involved in allogeneic skin graft rejection and provides another hint that CD26 deficiency leads to less rejection due to lower activation and proliferation of host immune cells.


DOI

doi:10.1038/s41423-018-0009-z