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Updated: Sep 24, 2025

Author Spotlight: Achieving High-Purity In Vitro Differentiation of Th17 Cells Using Cytokine Concentration Modulation
Published on: October 25, 2024
lncRNA STAT4-AS1 Inhibited TH17 Cell Differentiation by Targeting RORγt Protein
Hanlin He1, Xiangjie Qiu1, Mingming Qi2
1Department of Medical Microbiology, Central South University, Changsha, 410078 Hunan, China.
Objective:
From our previous study, we obtained long noncoding RNA (lncRNA) STAT4-AS1, which is related to asthma through high-throughput screening. However, we could not determine the specific mechanism involved and in response to this. We further designed this study.
Results:
First, we found that lncRNA STAT4-AS1 was downregulated in T cells from patients with asthma when compared to healthy controls. Next, we confirmed that lncRNA STAT4-AS1 was significantly negatively correlated with T helper 17 (TH17) differentiation in vitro experiments. The decreases of STAT4-AS1 promoted TH17 differentiation, while the increases of STAT4-AS1 inhibited TH17 differentiation. Subsequently, through RNA pull-down, RNA-binding protein immunoprecipitation (RIP), and dual luciferase reporter assay, we found that STAT4-AS1 could inhibit the binding of retinoid-related orphan receptor-γt (RORγt) protein with an IL-17A promoter after binding with RORγt protein. Fluorescence in situ hybridization (FISH) and nuclear-cytoplasmic separation assay showed that STAT4-AS1 is bonded to RORγt in the cytoplasm, preventing RORγt from entering the nucleus.
Conclusion:
Overall, STAT4-AS1 directly targets RORγt protein, inhibits the mutual binding of RORγt and IL-17 gene promoter, and eventually inhibits TH17 differentiation. To this end, STAT4-AS1 as a potential target may confer applications in the clinical treatment and diagnosis of TH17-related diseases.
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