Delayed allogeneic skin graft rejection in CD26-deficient mice

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.

Dipeptidyl peptidase 4 inhibitors and their potential immune modulatory functions

“…Moreover, CD26 knockout mice have been used to investigate the potential role of DPP4 in allogeneic skin graft rejection. It is shown that CD26 knockout mice display a reduced necrosis of grafts and a delayed graft rejection with significantly reduced secretion levels of the cytokines such as IFN-γ, IL-2, IL-6, IL-4, IL-17, and IL-13 but increased level of IL-10 after skin transplantation (Zhao et al, 2019). Additionally, a lower percentage of Th17 and CD8(+) T cells but a higher percentage of Treg cells are detected in peripheral blood lymphocytes of CD26 knockout mice in the same study (Zhao et al, 2019), indicating that CD26 deficiency leads to feebler rejection due to lower activation and less proliferation of host immune cells.…”

Involvement of CD26 in Differentiation and Functions of Th1 and Th17 Subpopulations of T Lymphocytes

“…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 to 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 [ 18 ]. In line with the results of these in vivo experiments, the results of the present in vitro study confirm that the expression of CD26 is not only highly correlated to the differentiation of Th1 and Th17 but also plays an important role in the functions of Th1 and Th17.…”

“…Recently, we have demonstrated a delayed allogeneic skin graft rejection in CD26-deficient mice. During graft rejection, 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 [ 18 ]. To further investigate the role of CD26 in the differentiation of Th17 subpopulations of human T lymphocytes, in this work, the correlation of CD26 expression with the differentiation of subsets of human T lymphocytes after solid-phase immobilized specific anti-CD3 mAb stimulation was investigated in vitro .…”

CD36himonocytes play immunoregulatory roles in human umbilical cord blood

“…CD26 is expressed at high level by several T cell subsets including Th17 cells [15] and mucosal-associated invariant T cells (MAIT cells) [16]. Gene knockout mouse studies indicate that CD26 plays both T cell activating [17] and modulatory functions [18].…”