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Journal of immunology research2026; 2026(1); e5310284; doi: 10.1155/jimr/5310284

Circulating Cell-Free RNA Reflects Immune-Associated and Airway Remodeling Signatures in Equine Asthma.

Abstract: Circulating cell-free RNA (cfRNA) has emerged as a promising minimally invasive biomarker capable of capturing transcripts originating from multiple tissues and cell types, but its utility in chronic inflammatory airway diseases remains poorly understood. Equine asthma (EA), a naturally occurring respiratory disease that shares key clinical and immunopathological features with human asthma, provides a valuable comparative model for evaluating plasma cfRNA in this context. We performed transcriptomic profiling of plasma cfRNA from horses with EA and healthy controls and compared these findings with partially matched bronchoalveolar lavage (BAL) and whole-blood (WB) transcriptomes. Differential abundance analysis of plasma cfRNA identified increased abundance of the epithelial alarmin IL33, together with signatures associated with tissue remodeling, cellular stress responses, and immune alterations. Notably, cfRNA from EA horses exhibited reduced B-cell-associated and increased T-cell-associated transcript signatures, a pattern independently supported by differential abundance, co-expression network, and deconvolution analyses. In contrast, similar immune-associated signatures were not evident in the BAL and WB transcriptomes analyzed in this study. Cross-compartment comparisons further demonstrated that plasma cfRNA captured a molecular profile largely distinct from those identified in BAL and WB, while sharing only a small set of differentially abundant transcripts across compartments. Collectively, these findings indicate that plasma cfRNA captures molecular patterns associated with EA that differ from those observed in conventional transcriptomic sampling compartments. These results support the potential utility of plasma cfRNA as a minimally invasive source of biomarkers for characterizing airway disease-associated molecular and immune alterations in both veterinary and comparative asthma research.
Copyright © 2026 Birong Zhang et al. Journal of Immunology Research published by John Wiley & Sons Ltd.
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Publication Date: 2026-08-26 PubMed ID: 42644703PubMed Central: PMC13509420DOI: 10.1155/jimr/5310284Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This study investigates how circulating cell-free RNA (cfRNA) in the blood plasma can reflect immune system changes and airway tissue remodeling in equine asthma, a horse respiratory disease similar to human asthma.
  • The research demonstrates that cfRNA profiles differ from those obtained through traditional sampling methods (bronchoalveolar lavage and whole blood), highlighting cfRNA as a novel, minimally invasive biomarker for airway disease.

Background and Rationale

  • Circulating cell-free RNA (cfRNA) refers to fragments of RNA freely circulating in the bloodstream, originating from various tissues and cells.
  • CfRNA is gaining interest as a minimally invasive biomarker because it can provide molecular insights without needing direct tissue sampling.
  • Chronic inflammatory airway diseases like asthma involve complex interactions of immune responses and tissue remodeling but the role of cfRNA in such diseases is not well established.
  • Equine asthma (EA) is a naturally occurring respiratory disease in horses sharing clinical and biological similarities with human asthma, making it an excellent comparative model.

Study Objective

  • To profile plasma cfRNA in horses with EA and compare it to healthy controls.
  • To compare cfRNA findings with transcriptomes from bronchoalveolar lavage (BAL) fluid and whole blood (WB) to understand how cfRNA signatures reflect airway disease.

Methodology

  • Plasma samples were collected from horses diagnosed with EA and from healthy controls.
  • Transcriptomic profiling of circulating cfRNA was performed to identify differences in RNA abundance between groups.
  • Transcriptomes from partially matched BAL fluid and whole blood samples were also analyzed to compare molecular signatures across compartments.
  • Analytical approaches included differential abundance analysis, co-expression network analysis, and immune cell deconvolution techniques.

Key Findings

  • Plasma cfRNA from EA horses showed elevated levels of IL33, an epithelial alarmin known to be involved in airway inflammation and remodeling.
  • Additional signatures related to tissue remodeling, cellular stress, and immune alterations were also identified in cfRNA profiles.
  • Immune cell signature shifts were observed in cfRNA: a decrease in B-cell-related transcripts and an increase in T-cell-related transcripts, indicating immune dysregulation.
  • These immune signature changes in cfRNA were supported by multiple independent analyses (differential abundance, network, deconvolution).
  • By contrast, immune-associated transcript changes seen in plasma cfRNA were not evident in either BAL or WB transcriptomes in this study.
  • Cross-comparisons showed that plasma cfRNA profiles largely represented molecular information distinct from BAL and WB, with only a small overlap in differentially abundant transcripts.

Interpretation and Implications

  • The study indicates that plasma cfRNA can reveal unique molecular patterns associated with EA that are not captured by conventional transcriptomic methods applied to airway fluid or blood cells.
  • Circulating cfRNA may provide information about both immune system changes and airway tissue remodeling in asthma without invasive sampling.
  • This suggests potential for cfRNA as a convenient, minimally invasive biomarker source to monitor airway disease severity, progression, or treatment response in veterinary medicine.
  • Due to the similarities between equine and human asthma, findings may inform biomarker development and disease understanding in human asthma research as well.

Conclusions

  • Plasma cfRNA is an informative biomarker reflecting immune and airway remodeling signatures in equine asthma.
  • CfRNA molecular profiles differ from those found in traditional compartments (BAL and whole blood), highlighting its complementary role.
  • These findings support further exploration of plasma cfRNA as a minimally invasive tool for studying and managing airway inflammatory diseases in both horses and possibly humans.

Cite This Article

APA
Zhang B, Agdour H, Riihimäki M, Hansen S, Raine A. (2026). Circulating Cell-Free RNA Reflects Immune-Associated and Airway Remodeling Signatures in Equine Asthma. J Immunol Res, 2026(1), e5310284. https://doi.org/10.1155/jimr/5310284

Publication

Journal of immunology research
ISSN: 2314-7156
NlmUniqueID: 101627166
Country: Egypt
Language: English
Volume: 2026
Issue: 1
Pages: e5310284
PII: 5310284

Researcher Affiliations

Zhang, Birong
  • Department of Medical Sciences, Uppsala University, Uppsala, Sweden, uu.se.
  • Science for Life Laboratory, Uppsala, Sweden, scilifelab.se.
Agdour, Hanna
  • Department of Medical Sciences, Uppsala University, Uppsala, Sweden, uu.se.
  • Science for Life Laboratory, Uppsala, Sweden, scilifelab.se.
Riihimäki, Miia
  • Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden, slu.se.
Hansen, Sanni
  • Department of Veterinary Clinical Sciences, University of Copenhagen, Copenhagen, Denmark, ku.dk.
Raine, Amanda
  • Department of Medical Sciences, Uppsala University, Uppsala, Sweden, uu.se.
  • Science for Life Laboratory, Uppsala, Sweden, scilifelab.se.

MeSH Terms

  • Animals
  • Horses
  • Asthma / immunology
  • Asthma / veterinary
  • Asthma / blood
  • Asthma / diagnosis
  • Asthma / genetics
  • Biomarkers / blood
  • Airway Remodeling / immunology
  • Airway Remodeling / genetics
  • Cell-Free Nucleic Acids / blood
  • Cell-Free Nucleic Acids / genetics
  • Horse Diseases / immunology
  • Horse Diseases / blood
  • Horse Diseases / diagnosis
  • Horse Diseases / genetics
  • Gene Expression Profiling
  • Transcriptome
  • Bronchoalveolar Lavage Fluid / immunology

Grant Funding

  • H-22-47-717 / Swedish-Norwegian Foundation for Equine Research
  • 2023-01377 / FORMAS
  • Uppsala Universitet

Conflict of Interest Statement

The authors declare no conflicts of interest.

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