The Effects of an IL-21 Receptor Antagonist on the Alloimmune Response in a Humanized Mouse Skin Transplant Model. Issue 10 (October 2019)

• Record Type: Journal Article
• Authors: de Leur, Kitty; Luk, Franka; van den Bosch, Thierry P.P.; Dieterich, Marjolein; van der Laan, Luc J.W.; Hendriks, Rudi W.; Clahsen-van Groningen, Marian C.; Issa, Fadi; Baan, Carla C.; Hoogduijn, Martin J.
• Is Part Of: Transplantation. Volume 103:Issue 10(2019)
• Publication Date: 2019-10
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; Transplantation immunology -- Periodicals; 617.95
• DOI: 10.1097/TP.0000000000002773
• Languages: English
• ISSNs: 0041-1337

Abstract

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. Abstract : Supplemental Digital Content is available in the text.