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Tofacitinib fails to prevent T cell transfer colitis in mice but ameliorates disease activity

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...

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Autores principales: Subramanyam, Sudheendra Hebbar, Hriczko, Judit Turyne, Pappas, Angeliki, Schippers, Angela, Wagner, Nobert, Ohl, Kim, Tenbrock, Klaus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9992375/
https://www.ncbi.nlm.nih.gov/pubmed/36882462
http://dx.doi.org/10.1038/s41598-023-30616-w
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author Subramanyam, Sudheendra Hebbar
Hriczko, Judit Turyne
Pappas, Angeliki
Schippers, Angela
Wagner, Nobert
Ohl, Kim
Tenbrock, Klaus
author_facet Subramanyam, Sudheendra Hebbar
Hriczko, Judit Turyne
Pappas, Angeliki
Schippers, Angela
Wagner, Nobert
Ohl, Kim
Tenbrock, Klaus
author_sort Subramanyam, Sudheendra Hebbar
collection PubMed
description 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.
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spelling pubmed-99923752023-03-09 Tofacitinib fails to prevent T cell transfer colitis in mice but ameliorates disease activity Subramanyam, Sudheendra Hebbar Hriczko, Judit Turyne Pappas, Angeliki Schippers, Angela Wagner, Nobert Ohl, Kim Tenbrock, Klaus Sci Rep Article 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. Nature Publishing Group UK 2023-03-07 /pmc/articles/PMC9992375/ /pubmed/36882462 http://dx.doi.org/10.1038/s41598-023-30616-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Subramanyam, Sudheendra Hebbar
Hriczko, Judit Turyne
Pappas, Angeliki
Schippers, Angela
Wagner, Nobert
Ohl, Kim
Tenbrock, Klaus
Tofacitinib fails to prevent T cell transfer colitis in mice but ameliorates disease activity
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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9992375/
https://www.ncbi.nlm.nih.gov/pubmed/36882462
http://dx.doi.org/10.1038/s41598-023-30616-w
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