RAGE antagonism with azeliragon improves xenograft rejection by T cells in humanized mice
Copyright © 2022 Elsevier Inc. All rights reserved.
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 245(2022) vom: 15. Dez., Seite 109165 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2022
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| Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't IL-17 Inflammation RAGE Rejection Xenograft Receptor for Advanced Glycation End Products Interleukin-17 azeliragon |
| Zusammenfassung: | Copyright © 2022 Elsevier Inc. All rights reserved. The receptor for advanced glycation endproducts (RAGE) is involved in multiple inflammatory processes. RAGE participates in adaptive and innate immune responses but its role in human immune cell responses has not been directly tested in vivo. We treated humanized mice (NSG) with the small molecule antagonist of RAGE, azeliragon, (AZ), and measured effects on xenogeneic (B6) skin graft rejection. AZ delayed the median time to xenograft rejection (22 vs 56 days, P = 0.0001). PD-1 expression on CD4+ and CD8+ T cells was lower following AZ therapy. Transcriptome studies showed inhibition of pathways in splenocytes with AZ including IL-23, IL-17A and IL-1β signaling. The serum levels of IL-1β and IL-17A in AZ treated mice were reduced in mice that did not reject skin grafts. The RAGE antagonist prevented xenograft rejection by human immune cells in a murine model. A RAGE antagonist may be a useful inhibitor of adaptive human immune responses |
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| Beschreibung: | Date Completed 25.11.2022 Date Revised 26.12.2022 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2022.109165 |