The low-density lipoprotein receptor-mTORC1 axis coordinates CD8+ T cell activation.
J Cell Biol
; 221(11)2022 11 07.
Article
in En
| MEDLINE
| ID: mdl-36129440
ABSTRACT
Activation of T cells relies on the availability of intracellular cholesterol for an effective response after stimulation. We investigated the contribution of cholesterol derived from extracellular uptake by the low-density lipoprotein (LDL) receptor in the immunometabolic response of T cells. By combining proteomics, gene expression profiling, and immunophenotyping, we described a unique role for cholesterol provided by the LDLR pathway in CD8+ T cell activation. mRNA and protein expression of LDLR was significantly increased in activated CD8+ compared to CD4+ WT T cells, and this resulted in a significant reduction of proliferation and cytokine production (IFNγ, Granzyme B, and Perforin) of CD8+ but not CD4+ T cells from Ldlr -/- mice after in vitro and in vivo stimulation. This effect was the consequence of altered cholesterol routing to the lysosome resulting in a lower mTORC1 activation. Similarly, CD8+ T cells from humans affected by familial hypercholesterolemia (FH) carrying a mutation on the LDLR gene showed reduced activation after an immune challenge.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptors, LDL
/
Lymphocyte Activation
/
Cholesterol
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CD8-Positive T-Lymphocytes
/
Mechanistic Target of Rapamycin Complex 1
Limits:
Animals
/
Humans
Language:
En
Journal:
J Cell Biol
Year:
2022
Document type:
Article
Affiliation country:
Italy