Mechanism of RNA‐Binding Protein ELAVL1 in Promoting Th2 Cell Differentiation Through Stabilizing CPA3 mRNA in Allergic Rhinitis

Abstract

ABSTRACT This study aimed to elucidate the role of the RNA‐binding protein embryonic lethality abnormal vision‐like protein 1 (ELAVL1) in the pathogenesis of allergic rhinitis (AR), specifically by investigating its potential to promote T helper 2 (Th2) cell differentiation by regulating the stability of carboxypeptidase A3 (CPA3) mRNA. Differentially expressed genes associated with AR were screened via bioinformatic analysis. Nasal mucosal tissues were collected from 42 children with AR and 42 healthy controls. CPA3 was significantly upregulated in the nasal mucosal tissues of AR patients. CD4+ T cells were isolated from the peripheral blood of healthy volunteers, polarized toward Th2 differentiation, and subjected to cell transfection experiments to examine the effect of CPA3 on Th2 differentiation. An ovalbumin (OVA)‐induced AR mouse model was established. Knockdown of CPA3 alleviated nasal symptoms (e.g., scratching and sneezing), attenuated pathological damage in the nasal mucosa (characterized by reduced edema and inflammatory cell infiltration), and suppressed Th2 immune responses (decreased interleukin‐4 and immunoglobulin E levels, reduced Th2 cell proportion, and downregulated GATA binding protein 3 expression) in AR mice. ELAVL1 bound to CPA3 mRNA and enhanced its stability, thereby upregulating CPA3 expression; a positive correlation was observed between their expression levels in AR. Overexpression of CPA3 reversed the alleviating effects of ELAVL1 knockdown on nasal symptoms and Th2 immune responses in AR mice. Taken together, these results demonstrate that targeting the ELAVL1/CPA3 axis may provide a novel therapeutic strategy for AR.