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Research Article: Exploration of miRNAs promoting eosinophilia and type 2 immunity

Date Published: 2026-09-25

Abstract:
MicroRNAs (miRNAs) are evolutionary conserved, small non-coding RNAs that regulate gene expression and modulate cellular responses. In this study, we profiled miRNAs regulated by interleukin-33 (IL-33), a key inflammatory mediator of allergic responses and type 2 immunity that promotes bone marrow eosinophil development and subsequent airway recruitment. C57BL/6 mice were exposed to recombinant IL-33 intranasally to induce airway eosinophilia. Cellular composition was determined by differential cell counts in bronchoalveolar lavage fluid and bone marrow. RNA profiling was performed using miRNA microarray, NanoString nCounter (miRNA and mRNA), qPCR (miRNA), and PrimeFlow—a method combining flow cytometry with single-cell miRNA detection. IL-33 challenge induced bone marrow eosinophilopoiesis and a significant influx of eosinophils into the airways. IL-33 altered miRNA expression in the lungs, displaying a distinct profile compared to IL-33-responsive miRNAs in the bone marrow. miRNAs previously implicated in regulating eosinophil development (e.g., miR-223-3p and miR-21) and type 2 lymphocyte effector functions (e.g., miR-155-5p, miR-150-5p) were significantly altered. These changes were accompanied by gene expression alterations in mediators associated with eosinophil migration (e.g., Il13ra1 , Il4ra and Csf2rb ). miR-150-5p was downregulated in the bone marrow of IL-33-challenged mice, and further single-cell analysis via PrimeFlow identified an enrichment of miR-150-5p expression in ILC2s. Furthermore, miR-150-5p targets expressed in ILC2s were modulated by IL-33, which induced high IL-5 production in bone marrow ILC2s. We identify candidate miRNA programs involved in the progression of IL-33-dependent eosinophilic inflammation from bone marrow induction to lung recruitment.

Introduction:
MicroRNAs (miRNAs) are evolutionary conserved, small non-coding RNAs that regulate gene expression and modulate cellular responses. In this study, we profiled miRNAs regulated by interleukin-33 (IL-33), a key inflammatory mediator of allergic responses and type 2 immunity that promotes bone marrow eosinophil development and subsequent airway recruitment.

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