Bone marrow CD8+ Trm cells induced by IL-15 and CD16+ monocytes contribute to HSPC destruction in human severe aplastic anemia.
Clin Immunol
; 263: 110223, 2024 Jun.
Article
in En
| MEDLINE
| ID: mdl-38636890
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hematopoietic Stem Cells
/
Monocytes
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Receptors, IgG
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CD8-Positive T-Lymphocytes
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Interleukin-15
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GPI-Linked Proteins
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Anemia, Aplastic
Limits:
Adolescent
/
Adult
/
Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
Clin Immunol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
United States