多胺
亚精胺
细胞生物学
生物
CD8型
T细胞
谷氨酰胺
精胺
腐胺
离体
细胞毒性T细胞
生物化学
免疫系统
体外
免疫学
酶
氨基酸
作者
Aya G. Elmarsafawi,Rebecca S. Hesterberg,Mario R. Fernandez,Chunying Yang,Lancia Darville,Min Liu,John M. Koomen,Otto Phanstiel,Reginald Atkins,John E. Mullinax,Shari Pilon‐Thomas,Frederick L. Locke,Pearlie K. Epling‐Burnette,John L. Cleveland
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2023-09-22
卷期号:8 (18)
标识
DOI:10.1172/jci.insight.169308
摘要
Glutaminolysis is a hallmark of the activation and metabolic reprogramming of T cells. Isotopic tracer analyses of antigen-activated effector CD8+ T cells revealed that glutamine is the principal carbon source for the biosynthesis of polyamines putrescine, spermidine, and spermine. These metabolites play critical roles in activation-induced T cell proliferation, as well as for the production of hypusine, which is derived from spermidine and is covalently linked to the translation elongation factor eukaryotic translation initiation factor 5A (eIF5A). Here, we demonstrated that the glutamine/polyamine/hypusine axis controlled the expression of CD69, an important regulator of tissue-resident memory T cells (Trm). Inhibition of this circuit augmented the development of Trm cells ex vivo and in vivo in the BM, a well-established niche for Trm cells. Furthermore, blocking the polyamine/hypusine axis augmented CD69 expression as well as IFN-γ and TNF-α production in (a) human CD8+ T cells from peripheral blood and sarcoma tumor infiltrating lymphocytes and (b) human CD8+ CAR-T cells. Collectively, these findings support the notion that the polyamine-hypusine circuit can be exploited to modulate Trm cells for therapeutic benefit.
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