Inflammatory factor-mediated miR-155/SOCS1 signaling axis leads to Treg impairment in systemic lupus erythematosus.
Int Immunopharmacol
; 141: 113013, 2024 Nov 15.
Article
in En
| MEDLINE
| ID: mdl-39213866
ABSTRACT
BACKGROUND:
Systemic lupus erythematosus (SLE) is an autoimmune disorder associated with the decrease and functional impairment of regulatory T cells (Tregs). In the current study, we explored the interplay of miR-155 and suppressor of cytokine signaling 1 (SOCS1) in regulating Treg function and stability in SLE.METHODS:
Clinical samples from healthy subjects and SLE patients were collected, and a mouse model of SLE was established to profile the expression pattern of miR-155 and SCOS1 in Tregs. Tregs isolated from mouse spleen were stimulated by inflammatory cytokines to confirm involvement of miR-155/SOCS1 axis in dictating Treg stability and function. We also administrated synthetic miR-155 inhibitor in SLE animal model to evaluate the potential effect on rescuing Treg function and alleviating SLE progression.RESULTS:
Tregs from SLE patients and SLE-induced mice exhibited a downregulation of SOCS1 and an upregulation of miR-155. In Tregs stimulated by inflammatory cytokines, Nuclear factor kappa B (NF-κB) signaling activation was required for the change of SOCS1 and miR-155 expression. miR-155 served as a negative regulator to dampen SOCS1 expression in inflammation-stimulated Tregs. The transfection of miR-155 mimic impaired the suppressive function and differentiation of Tregs through targeting SOCS1. In contrast, miR-155 inhibition improved Treg function under inflammatory stimulation and alleviated SLE conditions in the mouse model.CONCLUSION:
Inflammation-induced miR-155 impairs Treg stability and function in SLE through decreasing SOCS1 expression. Targeting miR-155 might be developed as an intervention to mitigate SLE conditions.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
T-Lymphocytes, Regulatory
/
MicroRNAs
/
Suppressor of Cytokine Signaling 1 Protein
/
Lupus Erythematosus, Systemic
Limits:
Adult
/
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
Int Immunopharmacol
Year:
2024
Document type:
Article