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

Journal article

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.

Authors: De Leur, K; Luk, F; Van Den Bosch, T; Dieterich, M; Van Der Laan, L

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Lippincott, Williams & Wilkins
• Journal: Transplantation
• Volume: 103
• Issue: 10
• Pages: 2065-2074
• Publication date: 2019-05-07
• DOI: 10.1097/tp.0000000000002773
• EISSN: 1534-6080
• ISSN: 0041-1337
• Pmid: 31343579
• Language: English
• Keywords: Journal Article