Abstract: TH-PO0397
RNA-Binding Protein Arid5a Drives Lupus Nephritis Progression by Regulating the Abnormal Differentiation of Tfh Cells
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
Author
- Zhang, Mingyang, Army Medical University, Chongqing, China
Background
The aberrant differentiation of Tfh cells plays a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE), particularly in driving excessive B cell activation. RNA-binding proteins (RBPs) regulate the fate of T cells, but the role of Arid5a in Tfh cell differentiation remains elusive.
Methods
The expression of Arid5a was analyzed in peripheral blood CD4+T cells of SLE patients. A Bm12-induced lupus mouse model, which is closely associated with Tfh cell differentiation, was employed. The mice were divided into three groups: a control group, a Bm12 group, and an Arid5a knockout + Bm12 group (generated by constructing CD4+T cell-specific Arid5a knockout mice and inducing the lupus model). Flow cytometry was used to detect changes in the frequency of various CD4+T cell subsets in each group. Furthermore, autoantibody levels, 24-hour urinary protein levels, and renal histopathological damage were assessed. RNA immunoprecipitation (RIP-seq) identified downstream key target genes bound by Arid5a.
Results
We analyzed RNA-seq data from PBMCs of SLE patients and found that, relative to healthy controls, the most significantly upregulated RBP in CD4+ T cells was Arid5a. Subsequent RT-qPCR analysis confirmed that Arid5a expression was significantly upregulated in peripheral blood CD4+ T cells of SLE patients. Arid5a expression was upregulated in CD4+ T cells of the Bm12 group compared to controls; conversely, the frequency of Tfh cells was significantly reduced in the Arid5a knockout + Bm12 group relative to the Bm12 group, with no significant alterations observed in other subsets. Additionally, serum levels of anti-dsDNA antibodies and IgG were significantly reduced, 24-hour urinary protein excretion decreased, and renal histopathological damage was ameliorated(Figure 1). RIP-seq results indicated that Arid5a could bind to the 3' UTR (Untranslated Region) of TCF-1 mRNA, and after Arid5a CKO, mRNA stability was reduced, but the transcriptional level of the TCF-1 gene showed no significant change(Figure 2).
Conclusion
Arid5a upregulates TCF-1 protein expression by enhancing the stability of TCF-1 mRNA, promoting the abnormal differentiation of SLE Tfh cells, ultimately driving disease progression. Targeting Arid5a may represent a novel therapeutic strategy for SLE.
Funding
- NIDDK Support