Abstract: TH-PO0400
Targeting FSTL1 Controls Lupus Nephritis by Promoting Treg Stability in Mice
Session Information
- Glomerular Diseases: Autoimmune Diseases
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Li, Yiqian, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
- Liu, Chi, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
Background
Immune dysregulation is one of the main causes of lupus nephritis (LN), and regulatory T (Treg) cells play an important role in the pathogenesis of LN. Recent studies have shown that Follistatin-like 1 (FSTL1) significantly promotes inflammation and fibrosis in kidney diseases and is elevated in various autoimmune disorders, highlighting its important role in immune regulation. However, whether FSTL1 is associated with the immune imbalance in LN has not been reported.
Methods
In this study, MRL/lpr spontaneous lupus mice were used as a model. Disease progression in the LN group was assessed by monitoring urinary creatinine and urinary protein weekly and calculating the urinary creatinine-to-protein ratio. Single-cell sequencing was further used to analyze the relationship between FSTL1 and proteins involved in Treg cells differentiation pathways. The proportion of Treg cells subsets and the expression levels of related cytokines, such as transforming growth factor-β (TGF-β) and interferon-γ (IFN-γ), were measured.
Results
Our findings indicate that FSTL1 may be a positive regulator of Treg cells differentiation. In CD4+ T cells from FSTL1-knockout mice, FSTL1 deficiency enhanced the expression of IL-17 and IL-6, inhibited Treg cells differentiation, and reduced IFN-γ production. Conversely, in CD4+ T cells from wild-type mice, FSTL1 activation promoted Treg cell differentiation. Furthermore, in CD4+ T cells isolated from LN mice, an FSTL1 agonist decreased the expression of IL-17 and RORγt and increased Foxp3 expression. Importantly, in vivo activation of Sirt-1 ameliorated LN by promoting cell differentiation, which was achieved through reducing the upregulated expression of SOCS3 in the LN kidneys.
Conclusion
In summary, Sirt-1 is a promising therapeutic target for controlling LN in a mouse model, suggesting that Sirt-1 may serve as a molecular target for LN treatment.
Funding
- Government Support – Non-U.S.