Ammonia detoxification promotes CD8+ T cell memory development by urea and citrulline cycles.
Nat Immunol
; 24(1): 162-173, 2023 01.
Article
en En
| MEDLINE
| ID: mdl-36471170
ABSTRACT
Amino acid metabolism is essential for cell survival, while the byproduct ammonia is toxic and can injure cellular longevity. Here we show that CD8+ memory T (TM) cells mobilize the carbamoyl phosphate (CP) metabolic pathway to clear ammonia, thus promoting memory development. CD8+ TM cells use ß-hydroxybutyrylation to upregulate CP synthetase 1 and trigger the CP metabolic cascade to form arginine in the cytosol. This cytosolic arginine is then translocated into the mitochondria where it is split by arginase 2 to urea and ornithine. Cytosolic arginine is also converted to nitric oxide and citrulline by nitric oxide synthases. Thus, both the urea and citrulline cycles are employed by CD8+ T cells to clear ammonia and enable memory development. This ammonia clearance machinery might be targeted to improve T cell-based cancer immunotherapies.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Citrulina
/
Amoníaco
Idioma:
En
Año:
2023
Tipo del documento:
Article