Metabolic modulation of mitochondrial mass during CD4+ T cell activation.
Cell Chem Biol
; 30(9): 1064-1075.e8, 2023 09 21.
Article
in En
| MEDLINE
| ID: mdl-37716347
ABSTRACT
Mitochondrial biogenesis initiates within hours of T cell receptor (TCR) engagement and is critical for T cell activation, function, and survival; yet, how metabolic programs support mitochondrial biogenesis during TCR signaling is not fully understood. Here, we performed a multiplexed metabolic chemical screen in CD4+ T lymphocytes to identify modulators of metabolism that impact mitochondrial mass during early T cell activation. Treatment of T cells with pyrvinium pamoate early during their activation blocks an increase in mitochondrial mass and results in reduced proliferation, skewed CD4+ T cell differentiation, and reduced cytokine production. Furthermore, administration of pyrvinium pamoate at the time of induction of experimental autoimmune encephalomyelitis, an experimental model of multiple sclerosis in mice, prevented the onset of clinical disease. Thus, modulation of mitochondrial biogenesis may provide a therapeutic strategy for modulating T cell immune responses.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Encephalomyelitis, Autoimmune, Experimental
Limits:
Animals
Language:
En
Journal:
Cell Chem Biol
Year:
2023
Document type:
Article
Affiliation country: