ORIGINAL RESEARCH article

Front. Allergy

Sec. Rhinology

Volume 6 - 2025 | doi: 10.3389/falgy.2025.1606255

This article is part of the Research TopicRecent Advances in Rhinology 2024View all 6 articles

Epigenetic Modifications are Associated with mRNA and Cytokine Expression Changes in Chronic Rhinosinusitis: A Multiomics Study from the United States

Provisionally accepted
Devyani  LalDevyani Lal1*Tripti  BrarTripti Brar1Chantal  MccabeChantal Mccabe2Erik  JessenErik Jessen2Nitish  KumarNitish Kumar1Pedro  Lança GomesPedro Lança Gomes1Michael  J MarinoMichael J Marino1Amar  MiglaniAmar Miglani1Hirohito  KitaHirohito Kita3
  • 1Department of Otolaryngology, Mayo Clinic in Arizona, Mayo Clinic Arizona, Scottsdale, Arizona, United States
  • 2Department of Health Sciences Research, Mayo Clinic, Rochester, Michigan, United States
  • 3Division of Allergy, Asthma and Clinical Immunology, Mayo Clinic Arizona, Scottsdale, Arizona, United States

The final, formatted version of the article will be published soon.

Objectives/Hypothesis: Chronic rhinosinusitis (CRS) may be triggered by environmental insults. We hypothesized that CRS results from epigenetic modifications of host DNA from external insults, leading to downstream RNA/DNA gene expression changes and immuno-mechanical disruptions. We therefore performed a multi-omics study integrating epigenetic (DNA methylation), transcriptomic (mRNA), and proteomic (cytokine) data of CRS sinonasal tissue to visualize interactions amongst these modalities to study our hypothesis. Methods: Sinonasal tissue was collected from 14 prospectively enrolled CRS and control subjects. Cytokine, mRNA transcriptome, and DNA methylome analysis were performed. Multi-omics analysis via joint dimensional reduction (JDR) was conducted.Results: Multi-omics unsupervised clustering separated subjects into two distinct groups: one cluster of 9 CRS subjects and another with 3 controls and 2 non-eosinophilic CRSsNP subjects. DNA methylation, followed by mRNA expression, contributed most to cluster assignment. DNA methylation was the most significant data modality contributing to total variance on JDR. Cytokines critical in CRS (IL-5, IL-13, IL-10, IFNγ, IL-6) associated with hundreds of differentially methylated regions (DMRs) and mRNA. On conjoint analyses, common upstream DMRs and mRNAs were linked to cytokines IL-5 and IL-13, cytokines IL-10 and IFNγ, and cytokines IFNγ and IL-6, respectively.Conclusions: Our results support the hypothesis that environmental insults may be significant drivers of CRS pathogenesis through epigenetic mechanisms that result in dysregulated mRNA transcription and cytokine expression. The most novel part of this study is our multi-omics approach that used integration of epigenetic (DNA methylation), transcriptomic (mRNA), and proteomic (cytokine) data to uncover insights into CRS pathogenesis; this is the first of its kind in CRS etiopathogenesis. The multi-omics analysis clearly separated clusters of control and CRS subjects, demonstrating its validity in future research. The study also identified interactions of methylated DNA, mRNA, and cytokines in CRS pathogenesis, highlighting novel molecules and pathways that may be potential therapeutic targets.

Keywords: epigenetics, Chronic rhinosinusitis, Transcriptomics, Proteomics, multiomics Cytokines Differentially Methylated DNA Differentially expressed mRNA IL-1RA SHANK2, STMND1, CD37, ANKRD65

Received: 04 Apr 2025; Accepted: 12 May 2025.

Copyright: © 2025 Lal, Brar, Mccabe, Jessen, Kumar, Gomes, Marino, Miglani and Kita. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Devyani Lal, Department of Otolaryngology, Mayo Clinic in Arizona, Mayo Clinic Arizona, Scottsdale, 85054, Arizona, United States

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