Sphingolipid biosynthesis is essential for metabolic rewiring during TH17 cell differentiation.
Sci Adv
; 10(17): eadk1045, 2024 Apr 26.
Article
in En
| MEDLINE
| ID: mdl-38657065
ABSTRACT
T helper 17 (TH17) cells are implicated in autoimmune diseases, and several metabolic processes are shown to be important for their development and function. In this study, we report an essential role for sphingolipids synthesized through the de novo pathway in TH17 cell development. Deficiency of SPTLC1, a major subunit of serine palmitoyl transferase enzyme complex that catalyzes the first and rate-limiting step of de novo sphingolipid synthesis, impaired glycolysis in differentiating TH17 cells by increasing intracellular reactive oxygen species (ROS) through enhancement of nicotinamide adenine dinucleotide phosphate oxidase 2 activity. Increased ROS leads to impaired activation of mammalian target of rapamycin C1 and reduced expression of hypoxia-inducible factor 1-alpha and c-Myc-induced glycolytic genes. SPTLCI deficiency protected mice from developing experimental autoimmune encephalomyelitis and experimental T cell transfer colitis. Our results thus show a critical role for de novo sphingolipid biosynthetic pathway in shaping adaptive immune responses with implications in autoimmune diseases.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sphingolipids
/
Cell Differentiation
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Encephalomyelitis, Autoimmune, Experimental
/
Serine C-Palmitoyltransferase
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Th17 Cells
Limits:
Animals
Language:
En
Journal:
Sci Adv
Year:
2024
Document type:
Article
Affiliation country: