Plant microRNAs as novel immunomodulatory agents
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Updated: Mar 21, 2026

MicroRNA Amplification and Recognition through Locked-nucleic-acid In situ Hybridization as a Novel Detection and Quantification Method
Published on: October 7, 2025
Duccio Cavalieri1,2, Lisa Rizzetto1, Noemi Tocci1
1Research and Innovation Centre, Fondazione Edmund Mach, via E. Mach 1, 38010 San Michele all'Adige (TN), Italy.
Abstract:
An increasing body of literature is addressing the immuno-modulating functions of miRNAs which include paracrine signaling via exosome-mediated intercellular miRNA. In view of the recent evidence of intake and bioavailability of dietary miRNAs in humans and animals we explored the immuno-modulating capacity of plant derived miRNAs. Here we show that transfection of synthetic miRNAs or native miRNA-enriched fractions obtained from a wide range of plant species and organs modifies dendritic cells ability to respond to inflammatory agents by limiting T cell proliferation and consequently dampening inflammation. This immuno-modulatory effect appears associated with binding of plant miRNA on TLR3 with ensuing impairment of TRIF signaling. Similarly, in vivo, plant small RNAs reduce the onset of severity of Experimental Autoimmune Encephalomyelities by limiting dendritic cell migration and dampening Th1 and Th17 responses in a Treg-independent manner. Our results indicate a potential for therapeutic use of plant miRNAs in the prevention of chronic-inflammation related diseases.
Insights
Plant-derived microRNAs (miRNAs) can dampen immune responses by modifying dendritic cell function. These findings suggest plant miRNAs hold therapeutic potential for chronic inflammatory diseases.
Area of Science:
- Immunology
- Molecular Biology
- Plant Science
Background:
- MicroRNAs (miRNAs) play crucial roles in immune modulation through intercellular communication.
- Dietary miRNAs have demonstrated intake and bioavailability in humans and animals.
- The immunomodulatory potential of plant-derived miRNAs remains largely unexplored.
Purpose of the Study:
- To investigate the immunomodulatory capacity of plant-derived miRNAs.
- To explore the therapeutic potential of plant miRNAs in inflammatory conditions.
Main Methods:
- Transfection of synthetic miRNAs and plant miRNA-enriched fractions into dendritic cells.
- Assessment of dendritic cell response to inflammatory agents.
- Evaluation of T cell proliferation and inflammatory markers.
- In vivo studies using Experimental Autoimmune Encephalomyelitis (EAE) models.
- Analysis of plant miRNA binding to Toll-like receptor 3 (TLR3) and downstream signaling pathways.
Main Results:
- Plant miRNAs, both synthetic and native, modulated dendritic cell responses, limiting T cell proliferation and reducing inflammation.
- The immunomodulatory effect was linked to plant miRNA binding to TLR3, impairing TRIF signaling.
- In vivo, plant small RNAs reduced EAE severity by inhibiting dendritic cell migration and dampening Th1/Th17 responses independently of Tregs.
Conclusions:
- Plant-derived miRNAs possess significant immunomodulatory properties.
- Plant miRNAs offer a potential therapeutic strategy for preventing and treating chronic inflammation-related diseases.
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