Novel janus kinase 3 inhibitor ritlecitinib suppresses T and B cell responses to prevent acute cardiac allograft rejection in mice
Copyright © 2025. Published by Elsevier Inc.
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 273(2025) vom: 15. Apr., Seite 110445 |
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| Weitere Verfasser: | , , , , , , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2025
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| Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
| Schlagworte: | Journal Article Acute rejection Cardiac transplantation Janus kinase 3 inhibitor Ritlecitinib (PF-06651600) T cell Janus Kinase 3 EC 2.7.10.2 Protein Kinase Inhibitors Cytokines |
| Zusammenfassung: | Copyright © 2025. Published by Elsevier Inc. Acute rejection is the main contributor to early allograft failure. Current immunosuppressive regimens have shortcomings, such as toxicity and minimal inhibitory effects on B cells. Hence, developing novel, effective, and selective anti-acute rejection drugs is crucial. Therefore, this study aimed to investigate the inhibitory effect of ritlecitinib (PF-06651600), a new janus kinase 3 inhibitor, on T and B cells, as well its preventive effects on acute allograft rejection. A murine cardiac transplantation model coupled with cell culture- and immunohistochemistry-based techniques was used. In vitro assays demonstrated that ritlecitinib inhibits naïve CD4+ T cell differentiation into T helper (Th)1 and Th17 cells, reduces relative inflammatory cytokines, and suppresses CD4+ and CD8+ T cell proliferation. Furthermore, ritlecitinib inhibited B cell activation and differentiation and antibody production. In vivo experiments revealed that ritlecitinib significantly prolongs allograft survival, decreases serum donor-specific antibody immunoglobulin G levels, alleviats allograft damage, and reduces C4d deposition and T, B, and plasma cell infiltration in allografts. Moreover, B and plasma cell percentages and counts were significantly decreased in recipient spleen, lymph nodes, bone marrow, and blood. Overall, ritlecitinib prevented acute rejection in cardiac transplantation by inhibiting T and B cells, suggesting its potential as a novel clinical immunosuppressant |
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| Beschreibung: | Date Completed 08.05.2025 Date Revised 08.05.2025 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2025.110445 |