Targeting miR-223 enhances myeloid-derived suppressor cell suppressive activities in multiple sclerosis patients.
Mult Scler Relat Disord
; 76: 104839, 2023 Aug.
Article
em En
| MEDLINE
| ID: mdl-37364375
ABSTRACT
BACKGROUND:
Multiple sclerosis (MS) is an incurable autoimmune inflammatory demyelinating disease of the central nervous system. Several MS medications can modify disease course through effects on adaptive immune cells, while drugs targeting innate immunity are under investigation. Myeloid-derived suppressor cells (MDSCs) which arise during chronic inflammation, are defined by their T-cell immunosuppressive functions. MiR-223 modulates myeloid cell maturation and expansion, including MDSCs.METHODS:
MDSCs isolated from healthy controls (HC) and people with MS (pwMS) were co-cultured with CD4+ T-cells to study their immunosuppressive activities in vitro. Cytokines and chemokines concentration were evaluated by Luminex assay in the serum of HC, pwMS, and other neuroinflammatory diseases and correlated with MDSC activities.RESULTS:
MDSC suppressive functions are dysregulated in pwMS compared to HC, which was reversed by glucocorticoids (GC). GC specifically downregulated miR-223 levels in MDSCs and increased the expression of STAT3. In vitro assay showed that miR-223 inhibition enhanced MDSC suppressive activity, STAT3 dependently. By multiple linear regression analysis, we demonstrated that MDSC phosphorylated STAT3 was correlated with serum GM-CSF in HC and pwMS.CONCLUSIONS:
These results suggest that miR-223 could be a therapeutic target for enhancing MDSC's suppressive activities as an alternative to GC.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
/
Células Supressoras Mieloides
/
Esclerose Múltipla
Limite:
Humans
Idioma:
En
Revista:
Mult Scler Relat Disord
Ano de publicação:
2023
Tipo de documento:
Article