Dual specificity protein phosphatase 5, transcriptionally inhibited by SRY-box transcription factor 11, inhibits T helper 2 differentiation in CD4+ T cells: a promising therapeutic target for allergic rhinitis.

Abstract

Allergic rhinitis (AR) is an inflammatory disorder driven primarily by aberrant T helper 2 (Th2) differentiation in CD4⁺ T cells. Although dual-specificity phosphatase 5 (DUSP5) has been implicated in inflammatory and autoimmune regulation, its role in AR remains unexplored. In this study, an AR mouse model was established via intraperitoneal sensitization and intranasal challenge with ovalbumin. We observed significant downregulation of DUSP5 expression in the nasal mucosa, particularly within CD4⁺ cells. To elucidate its function, a lentiviral vector overexpressing DUSP5 was constructed and used to transduce naive CD4⁺ T cells isolated from BALB/c mouse spleens. Overexpression of DUSP5 suppressed Th2-specific cytokine production and inhibited Th2 differentiation. Mechanistic investigations using a luciferase reporter assay revealed that Dusp5 is transcriptionally repressed by SRY-box transcription factor 11 (SOX11), a known transcription factor that promotes the progression of AR. Furthermore, DUSP5 overexpression counteracted the pro-Th2 effects mediated by SOX11. These results demonstrate that DUSP5, transcriptionally inhibited by SOX11, attenuates AR-associated inflammation by restraining Th2 differentiation. Our findings identify DUSP5 as a potential therapeutic target for AR.