Itaconate uptake via SLC13A3 improves hepatic antibacterial innate immunity.
Dev Cell
; 2024 Aug 03.
Article
de En
| MEDLINE
| ID: mdl-39116875
ABSTRACT
Itaconate is an immunoregulatory metabolite produced by the mitochondrial enzyme immune-responsive gene 1 (IRG1) in inflammatory macrophages. We recently identified an important mechanism by which itaconate is released from inflammatory macrophages. However, it remains unknown whether extracellular itaconate is taken up by non-myeloid cells to exert immunoregulatory functions. Here, we used a custom-designed CRISPR screen to identify the dicarboxylate transporter solute carrier family 13 member 3 (SLC13A3) as an itaconate importer and to characterize the role of SLC13A3 in itaconate-improved hepatic antibacterial innate immunity. Functionally, liver-specific deletion of Slc13a3 impairs hepatic antibacterial innate immunity in vivo and in vitro. Mechanistically, itaconate uptake via SLC13A3 induces transcription factor EB (TFEB)-dependent lysosomal biogenesis and subsequently improves antibacterial innate immunity in mouse hepatocytes. These findings identify SLC13A3 as a key itaconate importer in mouse hepatocytes and will aid in the development of potent itaconate-based antibacterial therapeutics.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Langue:
En
Journal:
Dev Cell
Sujet du journal:
EMBRIOLOGIA
Année:
2024
Type de document:
Article
Pays d'affiliation:
Chine
Pays de publication:
États-Unis d'Amérique