Usage Information
Citation Information: JCI Insight. 2023;8(18):e169308. https://doi.org/10.1172/jci.insight.169308.
Abstract
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.
Authors
Aya G. Elmarsafawi, Rebecca S. Hesterberg, Mario R. Fernandez, Chunying Yang, Lancia N.F. Darville, Min Liu, John M. Koomen, Otto Phanstiel IV, Reginald Atkins, John E. Mullinax, Shari A. Pilon-Thomas, Frederick L. Locke, Pearlie K. Epling-Burnette, John L. Cleveland
Usage data is cumulative from April 2024 through April 2025.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 1,595 | 411 |
| 195 | 110 | |
| Figure | 442 | 12 |
| Supplemental data | 105 | 14 |
| Citation downloads | 64 | 0 |
| Totals | 2,401 | 547 |
| Total Views | 2,948 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
