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De novo synthesis and salvage pathway coordinately regulate polyamine homeostasis and determine T cell proliferation and function
- Source :
- Science Advances
- Publication Year :
- 2020
-
Abstract
- Polyamine homeostasis determines T cell function.<br />Robust and effective T cell–mediated immune responses require proper allocation of metabolic resources through metabolic pathways to sustain the energetically costly immune response. As an essential class of polycationic metabolites ubiquitously present in all living organisms, the polyamine pool is tightly regulated by biosynthesis and salvage pathway. We demonstrated that arginine is a major carbon donor and glutamine is a minor carbon donor for polyamine biosynthesis in T cells. Accordingly, the dependence of T cells can be partially relieved by replenishing the polyamine pool. In response to the blockage of biosynthesis, T cells can rapidly restore the polyamine pool through a compensatory increase in extracellular polyamine uptake, indicating a layer of metabolic plasticity. Simultaneously blocking synthesis and uptake depletes the intracellular polyamine pool, inhibits T cell proliferation, and suppresses T cell inflammation, indicating the potential therapeutic value of targeting the polyamine pool for managing inflammatory and autoimmune diseases.
- Subjects :
- T cell
Immunology
Arginine
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Immune system
Extracellular
medicine
Polyamines
Homeostasis
Research Articles
030304 developmental biology
Cell Proliferation
0303 health sciences
Multidisciplinary
SciAdv r-articles
Cell Biology
Carbon
Cell biology
Glutamine
Metabolic pathway
medicine.anatomical_structure
chemistry
030220 oncology & carcinogenesis
Polyamine homeostasis
Polyamine
Intracellular
Research Article
Subjects
Details
- ISSN :
- 23752548
- Volume :
- 6
- Issue :
- 51
- Database :
- OpenAIRE
- Journal :
- Science advances
- Accession number :
- edsair.doi.dedup.....0647bb0d962af9bee48a9107da824ed2