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

Jie Long; Xing You; Qiong Yang; Song-Rong Wang; Ming Zhou; Wei Zhou; Caixia Wang; Huafeng Xie; Yuping Zhang; Shunqing Wang; Zhe-Xiong Lian; Liang Li

doi:10.1016/j.clim.2024.110223

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

Clin Immunol. 2024 Apr 16:263:110223. doi: 10.1016/j.clim.2024.110223. Online ahead of print.

Authors

Jie Long¹, Xing You², Qiong Yang³, Song-Rong Wang¹, Ming Zhou⁴, Wei Zhou⁴, Caixia Wang⁴, Huafeng Xie⁵, Yuping Zhang⁴, Shunqing Wang⁶, Zhe-Xiong Lian⁷, Liang Li⁸

Affiliations

¹ Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
² School of Medicine South China University of Technology, Guangzhou, China; Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
³ School of Medicine South China University of Technology, Guangzhou, China.
⁴ Department of Hematology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China.
⁵ Center for Medical Research on Innovation and Translation, Institute of Clinical Medicine, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China.
⁶ Department of Hematology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China. Electronic address: eywangshq@scut.edu.cn.
⁷ Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China. Electronic address: zxlian@gdph.org.cn.
⁸ Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China. Electronic address: liliang@gdph.org.cn.

PMID: 38636890
DOI: 10.1016/j.clim.2024.110223

Abstract

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.

Keywords: Aplastic anemia; Bone marrow; Monocytes; Single cell RNA sequencing; Tissue resident memory CD8(+)T cell.