Ruxolitinib attenuates acute rejection and can serve as an immune induction therapy in heart transplantation
Copyright © 2023. Published by Elsevier Inc.
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 257(2023) vom: 15. Dez., Seite 109851 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2023
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| Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't Heart transplantation IFN-γ signaling pathway Immunotherapy Single-cell RNA sequencing ruxolitinib 82S8X8XX8H Interleukin-2 Pyrazoles mehr... |
| Zusammenfassung: | Copyright © 2023. Published by Elsevier Inc. The benefits of IL2RA antagonists in heart transplant patients are controversial. We aimed to elucidate the effects of IL2RA antagonists and identify targets that could be better than IL2RA antagonists. By using single-cell RNA sequencing of immune cells at different time points in patients receiving IL2RA antagonists, we identified nineteen types of cells. We revealed higher IL2RA expression in regulatory T cells (Tregs), suggesting that IL2RA antagonists attenuated IL-2-induced Treg activation. CD4_C04_IFNGR1 and CD8_C05_IFITM2 which had more cytotoxic effects, remained elevated at later time points. IFNGR1 was upregulated in these two subtypes, but was not expressed in Treg. Ruxolitinib targeted the pathways of IFNGR1 (JAK1/2) while not affecting the pathway of IL-2-induced Tregs activation (JAK3). Ruxolitinib showed prolonged survival compared to IL2RA mAb-treated mice. Our study provided dynamic changes of immune cells after IL2RA antagonists treatment at single-cell resolution. Ruxolitinib has potential as a new immunoinduction therapy without affecting Treg |
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| Beschreibung: | Date Completed 16.12.2023 Date Revised 10.04.2024 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2023.109851 |