Polyamines from myeloid-derived suppressor cells promote Th17 polarization and disease progression.
Mol Ther
; 31(2): 569-584, 2023 02 01.
Article
in En
| MEDLINE
| ID: mdl-36307990
ABSTRACT
Myeloid-derived suppressor cells (MDSCs) are a group of immature myeloid cells that play an important role in diseases. MDSCs promote Th17 differentiation and aggravate systemic lupus erythematosus (SLE) progression by producing arginase-1 to metabolize arginine. However, the metabolic regulators remain unknown. Here, we report that MDSC derivative polyamines can promote Th17 differentiation via miR-542-5p in vitro. Th17 polarization was enhanced in response to polyamine treatment or upon miR-542-5p overexpression. The TGF-ß/SMAD3 pathway was shown to be involved in miR-542-5p-facilitated Th17 differentiation. Furthermore, miR-542-5p expression positively correlated with the levels of polyamine synthetases in peripheral blood mononuclear cells of patients with SLE as well as disease severity. In humanized SLE model mice, MDSC depletion decreased the levels of Th17 cells, accompanied by reduced expression of miR-542-5p and these polyamine synthetases. In addition, miR-542-5p expression positively correlated with the Th17 level and disease severity in both patients and humanized SLE mice. Together, our data reveal a novel molecular pathway by which MDSC-derived polyamine metabolism enhances Th17 differentiation and aggravates SLE.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
MicroRNAs
/
Myeloid-Derived Suppressor Cells
/
Lupus Erythematosus, Systemic
Limits:
Animals
Language:
En
Journal:
Mol Ther
Journal subject:
BIOLOGIA MOLECULAR
/
TERAPEUTICA
Year:
2023
Document type:
Article