Fludarabine Ameliorates Lupus Nephritis by Inhibiting T Cell Infiltration through STAT1 in R848-induced Mice Models
Se Gwang JANG 
The Rheumatism Research Center, The Catholic University, Seoul, Korea
Correspondence to: Se Gwang JANG
The Rheumatism Research Center, The Catholic University, Banpo-daero 222, Seocho-gu, Seoul 06591, Korea
E-mail: elite@catholic.ac.kr
ORCID: https://orcid.org/0000-0003-0518-5975
The Rheumatism Research Center, The Catholic University, Banpo-daero 222, Seocho-gu, Seoul 06591, Korea
E-mail: elite@catholic.ac.kr
ORCID: https://orcid.org/0000-0003-0518-5975
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
- Abstract
- Systemic lupus erythematosus (SLE) is a systemic autoimmune disease caused by both genetic and environmental factors. Fludarabine is a selective inhibitor of signal transducer and activator of transcription 1 (STAT1). Recently, STAT1 inhibitors have been considered potential treatments for SLE, due to the relationship between its pathogenesis and STAT1 pathway-mediated cytokines such as interferons. In the current study, we evaluated the therapeutic effects of fludarabine in an SLE animal model and explored its effects on T cell responses. 12-week-old C57BL/6 mice with topically administered R848 exhibited lupus-like phenotypes. Disease activity, such as proteinuria, autoantibody levels, immunoglobulin titers, the histological score, and C3 deposition, greatly improved with fludarabine treatment. In addition, fludarabine inhibited CD4+ T cells and T helper 1 (Th1) cells in the spleen and significantly decreased the differentiation of Th1 cells in vitro. These results indicate that Th1 cells play a critical role in the pathogenesis of lupus nephritis (LN). Thus, fludarabine exerted therapeutic effects on lupus animal models by suppressing Th1 cells via STAT1 inhibition. We propose that targeting STAT1 signaling using fludarabine could be an effective therapy for treating LN.
- Keywords : Fludarabine, R848-induced model, STAT1, Th1 cells
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Author ORCID Information-
- Se Gwang JANG
https://orcid.org/0000-0003-0518-5975
