Bone marrow CD8+ Trm cells induced by IL-15 and CD16+ monocytes contribute to HSPC destruction in human severe aplastic anemia

Bibliographische Detailangaben
Veröffentlicht in:	Clinical immunology (Orlando, Fla.). - 1999. - 263(2024) vom: 21. Juni, Seite 110223
1. Verfasser:	Long, Jie (VerfasserIn)
Weitere Verfasser:	You, Xing, Yang, Qiong, Wang, Song-Rong, Zhou, Ming, Zhou, Wei, Wang, Caixia, Xie, Huafeng, Zhang, Yuping, Wang, Shunqing, Lian, Zhe-Xiong, Li, Liang
Format:	Online-Aufsatz
Sprache:	English
Veröffentlicht:	2024
Zugriff auf das übergeordnete Werk:	Clinical immunology (Orlando, Fla.)
Schlagworte:	Journal Article Aplastic anemia Bone marrow Monocytes Single cell RNA sequencing Tissue resident memory CD8(+)T cell IL15 protein, human FCGR3B protein, human FASLG protein, human

Beschreibung
Zusammenfassung:	Copyright © 2024 Elsevier Inc. All rights reserved. Idiopathic severe aplastic anemia (SAA) is a disease of bone marrow failure caused by T-cell-induced destruction of hematopoietic stem and progenitor cells (HSPCs), however the mechanism remains unclear. We performed single-cell RNA sequencing of PBMCs and BMMCs from SAA patients and healthy donors and identified a CD8+ T cell subset with a tissue residency phenotype (Trm) in bone marrow that exhibit high IFN-γ and FasL expression and have a higher ability to induce apoptosis in HSPCs in vitro through FasL expression. CD8+ Trm cells were induced by IL-15 presented by IL-15Rα on monocytes, especially CD16+ monocytes, which were increased in SAA patients. CD16+ monocytes contributed to IL-15-induced CD38+CXCR6+ pre-Trm differentiation into CD8+ Trm cells, which can be inhibited by the CD38 inhibitor 78c. Our results demonstrate that IL-15-induced CD8+ Trm cells are pathogenic cells that mediate HSPC destruction in SAA patients and are therapeutic targets for future treatments
Beschreibung:	Date Completed 17.05.2024 Date Revised 22.08.2024 published: Print-Electronic Citation Status MEDLINE
ISSN:	1521-7035
DOI:	10.1016/j.clim.2024.110223