The effects of an IL-21 receptor antagonist on the alloimmune response in a humanized mouse skin transplant model
<br/><strong>Background: </strong>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 fur...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Lippincott, Williams & Wilkins
2019
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| _version_ | 1797082573631913984 |
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| author | De Leur, K Luk, F Van Den Bosch, T Dieterich, M Van Der Laan, L Hendriks, R Groningen, C Issa, F Baan, C Hoogduijn, M |
| author_facet | De Leur, K Luk, F Van Den Bosch, T Dieterich, M Van Der Laan, L Hendriks, R Groningen, C Issa, F Baan, C Hoogduijn, M |
| author_sort | De Leur, K |
| collection | OXFORD |
| description | <br/><strong>Background: </strong>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.<br/><strong>Methods: </strong>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).<br/><strong>Results: </strong>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.<br/><strong>Conclusion: </strong>These findings demonstrate that blockade of IL-21 signaling can delay allograft rejection in a humanized skin transplantation model. |
| first_indexed | 2024-03-07T01:29:50Z |
| format | Journal article |
| id | oxford-uuid:933aef18-ba00-4936-99eb-cafb132d9733 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:29:50Z |
| publishDate | 2019 |
| publisher | Lippincott, Williams & Wilkins |
| record_format | dspace |
| spelling | oxford-uuid:933aef18-ba00-4936-99eb-cafb132d97332022-03-26T23:30:51ZThe effects of an IL-21 receptor antagonist on the alloimmune response in a humanized mouse skin transplant modelJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:933aef18-ba00-4936-99eb-cafb132d9733EnglishSymplectic Elements at OxfordLippincott, Williams & Wilkins2019De Leur, KLuk, FVan Den Bosch, TDieterich, MVan Der Laan, LHendriks, RGroningen, CIssa, FBaan, CHoogduijn, M<br/><strong>Background: </strong>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.<br/><strong>Methods: </strong>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).<br/><strong>Results: </strong>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.<br/><strong>Conclusion: </strong>These findings demonstrate that blockade of IL-21 signaling can delay allograft rejection in a humanized skin transplantation model. |
| spellingShingle | De Leur, K Luk, F Van Den Bosch, T Dieterich, M Van Der Laan, L Hendriks, R Groningen, C Issa, F Baan, C Hoogduijn, M The effects of an IL-21 receptor antagonist on the alloimmune response in a humanized mouse skin transplant model |
| title | The effects of an IL-21 receptor antagonist on the alloimmune response in a humanized mouse skin transplant model |
| title_full | The effects of an IL-21 receptor antagonist on the alloimmune response in a humanized mouse skin transplant model |
| title_fullStr | The effects of an IL-21 receptor antagonist on the alloimmune response in a humanized mouse skin transplant model |
| title_full_unstemmed | The effects of an IL-21 receptor antagonist on the alloimmune response in a humanized mouse skin transplant model |
| title_short | The effects of an IL-21 receptor antagonist on the alloimmune response in a humanized mouse skin transplant model |
| title_sort | effects of an il 21 receptor antagonist on the alloimmune response in a humanized mouse skin transplant model |
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