BATF/RORgt/IL-17 Axis as a Therapeutic Target in Systemic Lupus Erythematosus: Integrative Bioinformatics and In Vivo Validation of Langchuangding Combined with Prednisone

Abstract

Background: Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disease characterized by aberrant Th17/Treg balance and autoantibody production. While glucocorticoids remain the cornerstone of treatment, their long-term adverse effects necessitate the development of steroid-sparing agents. The basic leucine zipper transcription factor ATF-like (BATF) serves as an essential pioneer factor for Th17 differentiation, yet its precise therapeutic potential in SLE remains underexplored. This study aims to validate the BATF/RORgt/IL-17 axis as a critical therapeutic target in SLE through integrative bioinformatics analysis of human cohorts and in vivo experimental validation using a combined regimen of Traditional Chinese Medicine (Langchuangding, LCD) and Prednisone. Methods: Transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from 61 SLE patients and 20 healthy controls (HC) were retrieved from the Gene Expression Omnibus (GEO: GSE50772). Differentially expressed genes (DEGs) and immune pathway signatures were analyzed. For in vivo validation, 40 female MRL/lpr mice (SLE model) and 10 normal Kunming mice were randomly divided into five groups.  Over a 10-week intervention, body weight and organ indices were monitored.         The mRNA and protein expression levels of BATF, RORgt (Rorc), and IL-17 in renal tissues were quantified using qPCR and ELISA. Serum autoantibodies (ANA, anti-dsDNA, anti-Sm-DNA) were also measured. Results: Bioinformatics analysis revealed significant upregulation of BCL6 and IL10 in SLE PBMCs, alongside a global interferon signature, establishing a pronounced systemic inflammatory state. In MRL/lpr mice, the Model group exhibited severe splenomegaly, elevated autoantibodies, and robust overexpression of renal BATF, RORgt, and IL-17. The Combined therapy (LCD + Prednisone) demonstrated superior efficacy, significantly attenuating body weight loss, normalizing spleen indices, and drastically suppressing the BATF/RORgt/IL-17 cascade at both transcriptional and translational levels (p < 0.001 vs. Model). Serum ANA, anti-dsDNA, and anti-Sm-DNA levels were also maximally reduced in the Combined group.     Conclusion: The BATF/RORgt/IL-17 axis is a pivotal pathogenic driver in SLE, bridging epigenetic chromatin remodeling with downstream Th17-mediated  autoimmunity. The synergistic application of LCD and Prednisone effectively dismantles this axis, offering a promising steroid-sparing, individualized therapeutic strategy for SLE management.