The effects of an IL-21 receptor antagonist on the alloimmune response in a humanized mouse skin transplant model

Background: Interleukin 21 (IL-21) is involved in regulating the expansion and effector function of a broad range of leukocytes, including T cells and B cells. In transplantation, the exact role of IL-21 in the process of allograft rejection is unknown. To further explore this, the aim of this study is to test the effect of an IL-21 receptor (IL-21R) blocking antibody on the early phase of allograft rejection in a humanized skin transplantation model in mice reconstituted with human T and B cells.Methods: Immunodeficient Balb/c IL2rγ-/-Rag2-/- mice were transplanted with human skin followed by adoptive transfer of human allogeneic splenocytes. Control animals were treated with a PBS vehicle while the other group was treated with a humanized anti-IL-21R antibody (αIL-21R).Results: In the PBS treated animals, human skin allografts were infiltrated with lymphocytes and developed a thickened epidermis with increased expression of the inflammatory markers Keratin 17 (Ker17) and Ki67. In mice treated with αIL-21R, these signs of allograft reactivity were significantly reduced. Concordantly, STAT3 phosphorylation was inhibited in this group. Of note, treatment with αIL-21R attenuated the process of T and B cell reconstitution after adoptive cellular transfer.Conclusion: These findings demonstrate that blockade of IL-21 signaling can delay allograft rejection in a humanized skin transplantation model.</br

The effects of an IL-21 receptor antagonist on the alloimmune response in a humanized mouse skin transplant model

Background: Interleukin 21 (IL-21) is involved in regulating the expansion and effector function of a broad range of leukocytes, including T cells and B cells. In transplantation, the exact role of IL-21 in the process of allograft rejection is unknown. To further explore this, the aim of this study is to test the effect of an IL-21 receptor (IL-21R) blocking antibody on the early phase of allograft rejection in a humanized skin transplantation model in mice reconstituted with human T and B cells.Methods: Immunodeficient Balb/c IL2rγ-/-Rag2-/- mice were transplanted with human skin followed by adoptive transfer of human allogeneic splenocytes. Control animals were treated with a PBS vehicle while the other group was treated with a humanized anti-IL-21R antibody (αIL-21R).Results: In the PBS treated animals, human skin allografts were infiltrated with lymphocytes and developed a thickened epidermis with increased expression of the inflammatory markers Keratin 17 (Ker17) and Ki67. In mice treated with αIL-21R, these signs of allograft reactivity were significantly reduced. Concordantly, STAT3 phosphorylation was inhibited in this group. Of note, treatment with αIL-21R attenuated the process of T and B cell reconstitution after adoptive cellular transfer.Conclusion: These findings demonstrate that blockade of IL-21 signaling can delay allograft rejection in a humanized skin transplantation model

The emergence of regenerative medicine in organ transplantation: 1st European Cell Therapy and Organ Regeneration Section meeting.

Regenerative medicine is emerging as a novel field in organ transplantation. In September 2019, the European Cell Therapy and Organ Regeneration Section (ECTORS) of the European Society for Organ Transplantation (ESOT) held its first meeting to discuss the state-of-the-art of regenerative medicine in organ transplantation. The present article highlights the key areas of interest and major advances in this multidisciplinary field in organ regeneration and discusses its implications for the future of organ transplantation