Tofacitinib fails to prevent T cell transfer colitis in mice but ameliorates disease activity
Abstract Tofactinib is a JAK inhibitor approved for ulcerative colitis in humans. Despite of its’ proven effectiveness in humans, mechanistic data are scarce on the effectiveness of Tofactinib in experimental colitis in mice. We induced experimental colitis by transfer of CD4+CD25− isolated T cells...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-30616-w |
| _version_ | 1827984354866888704 |
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| author | Sudheendra Hebbar Subramanyam Judit Turyne Hriczko Angeliki Pappas Angela Schippers Nobert Wagner Kim Ohl Klaus Tenbrock |
| author_facet | Sudheendra Hebbar Subramanyam Judit Turyne Hriczko Angeliki Pappas Angela Schippers Nobert Wagner Kim Ohl Klaus Tenbrock |
| author_sort | Sudheendra Hebbar Subramanyam |
| collection | DOAJ |
| description | Abstract Tofactinib is a JAK inhibitor approved for ulcerative colitis in humans. Despite of its’ proven effectiveness in humans, mechanistic data are scarce on the effectiveness of Tofactinib in experimental colitis in mice. We induced experimental colitis by transfer of CD4+CD25− isolated T cells into RAG2−/− (T and B cell deficient) mice and treated these mice with tofacitinib for 5–6 weeks either with a dosage of 10 or 40 mg/kg body weight immediately after CD4+ transfer or started treatment after first symptoms of disease for several weeks. While treatment with tofacitinib immediately after transfer resulted in an enhanced expansion of CD4+ T cells and did not prevent occurrence of colitis, treatment after start of symptoms of colitis ameliorated disease activity on a clinical basis and in histological analyses. Tofacitinib is effective in the treatment of murine experimental T cell transfer colitis, however does not prevent occurrence of disease. |
| first_indexed | 2024-04-09T22:58:59Z |
| format | Article |
| id | doaj.art-fd2696ae3047486a812ed569421d260d |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T22:58:59Z |
| publishDate | 2023-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-fd2696ae3047486a812ed569421d260d2023-03-22T11:09:31ZengNature PortfolioScientific Reports2045-23222023-03-0113111010.1038/s41598-023-30616-wTofacitinib fails to prevent T cell transfer colitis in mice but ameliorates disease activitySudheendra Hebbar Subramanyam0Judit Turyne Hriczko1Angeliki Pappas2Angela Schippers3Nobert Wagner4Kim Ohl5Klaus Tenbrock6Department of Pediatrics, RWTH Aachen UniversityDepartment of Pediatrics, RWTH Aachen UniversityDepartment of Pediatrics, RWTH Aachen UniversityDepartment of Pediatrics, RWTH Aachen UniversityDepartment of Pediatrics, RWTH Aachen UniversityDepartment of Pediatrics, RWTH Aachen UniversityDepartment of Pediatrics, RWTH Aachen UniversityAbstract Tofactinib is a JAK inhibitor approved for ulcerative colitis in humans. Despite of its’ proven effectiveness in humans, mechanistic data are scarce on the effectiveness of Tofactinib in experimental colitis in mice. We induced experimental colitis by transfer of CD4+CD25− isolated T cells into RAG2−/− (T and B cell deficient) mice and treated these mice with tofacitinib for 5–6 weeks either with a dosage of 10 or 40 mg/kg body weight immediately after CD4+ transfer or started treatment after first symptoms of disease for several weeks. While treatment with tofacitinib immediately after transfer resulted in an enhanced expansion of CD4+ T cells and did not prevent occurrence of colitis, treatment after start of symptoms of colitis ameliorated disease activity on a clinical basis and in histological analyses. Tofacitinib is effective in the treatment of murine experimental T cell transfer colitis, however does not prevent occurrence of disease.https://doi.org/10.1038/s41598-023-30616-w |
| spellingShingle | Sudheendra Hebbar Subramanyam Judit Turyne Hriczko Angeliki Pappas Angela Schippers Nobert Wagner Kim Ohl Klaus Tenbrock Tofacitinib fails to prevent T cell transfer colitis in mice but ameliorates disease activity Scientific Reports |
| title | Tofacitinib fails to prevent T cell transfer colitis in mice but ameliorates disease activity |
| title_full | Tofacitinib fails to prevent T cell transfer colitis in mice but ameliorates disease activity |
| title_fullStr | Tofacitinib fails to prevent T cell transfer colitis in mice but ameliorates disease activity |
| title_full_unstemmed | Tofacitinib fails to prevent T cell transfer colitis in mice but ameliorates disease activity |
| title_short | Tofacitinib fails to prevent T cell transfer colitis in mice but ameliorates disease activity |
| title_sort | tofacitinib fails to prevent t cell transfer colitis in mice but ameliorates disease activity |
| url | https://doi.org/10.1038/s41598-023-30616-w |
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