The effects of an IL-21 receptor antagonist on the alloimmune response in a humanized mouse skin transplant model
K de Leur, F Luk, TPP van den Bosch, M Dieterich… - …, 2019 - journals.lww.com
Transplantation, 2019•journals.lww.com
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 …
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 …
Abstract
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 phosphate buffered saline vehicle while the other group was treated with a humanized anti-IL-21R antibody (αIL-21R).
Results.
In the phosphate buffered saline-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.
Conclusions.
These findings demonstrate that blockade of IL-21 signaling can delay allograft rejection in a humanized skin transplantation model.
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