SHR0302 Improves Treg/Th17 Imbalance in Patients with Systemic Lupus Erythematosus

• Published in: Indian journal of clinical biochemistry Vol. 40; no. 2; pp. 274 - 283
• Main Authors: Mohammad, Talar Ahmad Merza, Jaafar, Halmat M., Maroof, Avin Mohammad Arif
• Format: Journal Article
• Language: English
• Published: New Delhi Springer India 01.04.2025; Springer Nature B.V
• Subjects: Autoimmune diseases; Biochemistry; Biomedical and Life Sciences; CD25 antigen; CD4 antigen; Chemistry/Food Science; Cytokines; Flow cytometry; Foxp3 protein; Gene expression; Helper cells; Inflammation; Interferon regulatory factor 4; Interleukin 10; Interleukin 21; Interleukin 6; Janus kinase; Life Sciences; Lupus; Lymphocytes T; Microbiology; Original Research Article; Pathology; Signal transduction; Stat3 protein; Systemic lupus erythematosus; Tumor necrosis factor-α; γ-Interferon; Systemic lupus erythematous; Treg/Th17 imbalance; SHR0302
• ISSN: 0970-1915; 0974-0422
• DOI: 10.1007/s12291-023-01179-4

IL-6-mediated JAK1/STAT3 signaling pathway is involved in the development of Th17 cells, which play an essential role in the pathogenesis of various autoimmune diseases such as systemic lupus erythematosus (SLE). To evaluation of the regulatory and anti-inflammatory effects of the JAK1/STAT3 inhibition in SLE, we evaluated the effects of SHR0302 on regulatory T cell (Treg)/Th17 balance. Thirty-two patients with SLE and twenty-nine healthy subjects were enrolled in this study. The mRNA expression levels of anti- and pro-inflammatory cytokines, such as FOXP3, ROR-γt, IL-10, IL-17A, IL-21, and IRF-4, were determined using real-time PCR, and the cytokine levels of IL-6, IL-10, IL-17A, TNF-α, and IFN-γ were analyzed by ELISA. The frequency and in vitro development of CD4+ CD25+ Foxp3+ Treg and Th17 cells were evaluated by flow cytometry. SHR0302 could increase the mRNA expression and cytokine level of Treg-related molecules. Furthermore, numbers of Treg cells were increased, after treatment with SHR0302. In contrast, the mRNA expression level of Th17-related molecules, ROR-γt, IL-17A, and IL-21, were decreased. Reduction of inflammatory cytokine levels was a confirmation of the modulating effect of the SHR0302, including IL-6, IL-17, TNF-α, and IFN-γ. In addition, frequency of Th17 cells were reduced by SHR0302. Our study shows that SHR0302 regulating the JAK1/STAT3 pathway can be a new treatment option for SLE.