MicroRNA-4497 Is Downregulated in Pediatric Allergic Diseases and Suppresses Th2 Inflammation in an Animal Model.

Abstract

Introduction: Atopic dermatitis (AD), allergic rhinitis (AR), and bronchial asthma (BA) are major allergic diseases in childhood. Pediatric allergic diseases are characterized by the "atopic march," where two or more allergic conditions can occur either simultaneously or sequentially. MicroRNAs (miRNAs) serve as fine regulators of gene expression, capable of modulating the clinical manifestations of allergic diseases posttranscriptionally. We investigated miRNAs commonly expressed in these three allergic diseases to enhance the understanding of their development and management.

Methods: We collected serum samples from subjects diagnosed with AD, AR, and BA as well as from healthy controls at Korea University Anam Hospital. Their miRNA expression patterns were analyzed using microarray technology. Additionally, we examined the allergic inflammatory response of miRNA through an allergic animal model.

Results: A total of 68 subjects were enrolled in the allergy group, consisting of 42 with AD, 13 with AR, and 13 with BA, while 10 children participated as controls. Microarray analysis revealed that miR-4497 expression levels were consistently downregulated in these three allergic disease groups. Following mast cell activation and miR-4497 transfection, reduced levels of macrophage-derived chemokines (MDCs) were observed. Furthermore, levels of IL-4, MDC, and methacholine Penh were significantly decreased in a miR-4497-treated mouse model.

Conclusions: MiR-4497 expressions were consistently downregulated in pediatric subjects with AD, AR, and BA. Allergic inflammation was significantly reduced in human mast cell-1 transfected with miR-4497 and in the treated mouse model. Further research is needed to elucidate the epigenetic mechanisms by which miR-4497 modulates allergic diseases and to explore its potential as a noninvasive biomarker for diagnosis and treatment.