The IL-23p19 monoclonal antibody significantly alleviates nephritis in MRL/lpr lupus mice by modulating the Th17/Treg balance.
- Author:
Wei CHENG
1
;
Saizhe SONG
2
;
Yu SHEN
2
;
Cuiping LIU
2
;
Xin CHANG
3
;
Jian WU
4
Author Information
1. Department of Rheumatology and Immunology, The First Affiliated Hospital of Soochow University, Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou 215006; Department of Dermatology, Changshu No. 2 People's Hospital, Suzhou 215501, China.
2. Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
3. Department of Rheumatology and Immunology, The First Affiliated Hospital of Soochow University, Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
4. Department of Rheumatology and Immunology, The First Affiliated Hospital of Soochow University, Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China. *Corresponding author, E-mail: wujian001@suda.edu.cn.
- Publication Type:Journal Article
- MeSH:
Animals;
Female;
Mice, Inbred MRL lpr;
T-Lymphocytes, Regulatory/drug effects*;
Th17 Cells/drug effects*;
Antibodies, Monoclonal/therapeutic use*;
Interleukin-23 Subunit p19/immunology*;
Mice;
Lupus Nephritis/drug therapy*;
Kidney/drug effects*;
Antibodies, Antinuclear/blood*
- From:
Chinese Journal of Cellular and Molecular Immunology
2025;41(7):620-628
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the therapeutic effects of interleukin 23p19(IL-23p19) monoclonal antibody in the MRL/lpr lupus-like mouse model. Methods A total of 36 female MRL/lpr mice aged 8 weeks were randomly divided into 6 groups: PBS group (blank control), IgG group (isotype IgG), dexamethasone (DEX) group (positive control), and three IL-23p19 monoclonal antibody treatment groups with different dose gradients: low dose (LD, 1 mg/kg), medium dose (MD, 3 mg/kg), and high dose (HD, 10 mg/kg). Drug intervention began at 12 weeks of age via tail vein injection. Urine protein levels were measured using urine protein test strips; serum anti-dsDNA antibody levels were detected by ELISA; serum creatinine and blood urea nitrogen levels were measured using an automatic biochemical analyzer; renal histopathological changes were analyzed by H&E and PAS staining; immunofluorescence was used to assess IgG and C3 immune complex deposition in kidney tissues; flow cytometry was employed to examine the expression of T helper 1(Th1), Th2, Th17, T follicular helper (Tfh), and regulatory T cells(Treg) cell subsets in the spleen; and RT-qPCR was used to detect the expression of related transcription factors in the spleen. Results IL-23p19 monoclonal antibody reduced urine protein levels, alleviated splenomegaly, improved renal function, and decreased anti-dsDNA antibody levels in MRL/lpr mice. It also mitigated glomerulonephritis and reduced renal immune complex deposition. Furthermore, IL-23p19 monoclonal antibody significantly suppressed the proportion of Th1 and Th17 cells while upregulating Treg cell proportion in the spleen. Additionally, it downregulated T-bet and retinoic acid receptor-related orphan receptor γt (RORγt) mRNA levels and upregulated forkhead box P3(FOXP3) mRNA levels in the spleen. Conclusions IL-23p19 monoclonal antibody demonstrates significant therapeutic effects in MRL/lpr mice, likely through modulation of the Th17/Treg cell balance.
