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Plant microRNAs as novel immunomodulatory agents.

Cavalieri D, Rizzetto L, Tocci N, Rivero D, Asquini E, Si-Ammour A, Bonechi E, Ballerini C, Viola R - Sci Rep (2016)

Bottom Line: An increasing body of literature is addressing the immuno-modulating functions of miRNAs which include paracrine signaling via exosome-mediated intercellular miRNA.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.

View Article: PubMed Central - PubMed

Affiliation: Research 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.

No MeSH data available.


Related in: MedlinePlus

Effects of different plant sRNA extracts on T cell proliferation.(a–d) T cells were exposed to DCs, in presence or not of FvmiR146, bolmiR874 or osamiR168 (10 ng/ml, (a), F. vesca total sRNA (b) or human and B. taurus total sRNA (10 ng/ml, (c) or sRNA fractions obtained as described in Material and Methods section (10 ng/ml, (d) or B. taurus total and 10–60 nt sRNA fraction (e), and LPS (10 ng/ml). Fractioning of sRNA has been performed by polyacrylamide electrophoresis separation. Panel (d) refers to the results obtained using 10–60 nt sRNA, 70–100 nt sRNA and 100–150 nt sRNA. After five days of T cells-DCs co-cultures, proliferation has been measured as [3H]-Thy uptake by liquid scintillation [3H]-Thy. MLR results are shown. Proliferation is presented as stimulation index, Percentage Stimulation above background is determined for each stimulated sample, through comparison with results from an unstimulated sample. Mean ± SD, N = 6, *p < 0.05, **p < 0.01, Kruskal Wallis, pretreatment (+miRNA duplexes or sRNA fractions) vs not-pretreated cells (none).
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f4: Effects of different plant sRNA extracts on T cell proliferation.(a–d) T cells were exposed to DCs, in presence or not of FvmiR146, bolmiR874 or osamiR168 (10 ng/ml, (a), F. vesca total sRNA (b) or human and B. taurus total sRNA (10 ng/ml, (c) or sRNA fractions obtained as described in Material and Methods section (10 ng/ml, (d) or B. taurus total and 10–60 nt sRNA fraction (e), and LPS (10 ng/ml). Fractioning of sRNA has been performed by polyacrylamide electrophoresis separation. Panel (d) refers to the results obtained using 10–60 nt sRNA, 70–100 nt sRNA and 100–150 nt sRNA. After five days of T cells-DCs co-cultures, proliferation has been measured as [3H]-Thy uptake by liquid scintillation [3H]-Thy. MLR results are shown. Proliferation is presented as stimulation index, Percentage Stimulation above background is determined for each stimulated sample, through comparison with results from an unstimulated sample. Mean ± SD, N = 6, *p < 0.05, **p < 0.01, Kruskal Wallis, pretreatment (+miRNA duplexes or sRNA fractions) vs not-pretreated cells (none).

Mentions: Given that dsRNA binding to TLR3 is not sequence-dependent, we tested whether the anti-inflammatory efficacy shown by FvmiR168 could also be observed with other miRNAs such as FvmiR156, another abundant strawberry miRNA, bolmiR874 an abundant cabbage miRNA or osamiR168 from rice, the plant miRNA detected in blood plasma of human and animal subjects after dietary consumption of rice29. DCs treatment with synthetic equivalents of these plant miRNAs reduced T cell proliferation to a similar extent than FvmiR168 (Fig. 4a, p < 0.01).


Plant microRNAs as novel immunomodulatory agents.

Cavalieri D, Rizzetto L, Tocci N, Rivero D, Asquini E, Si-Ammour A, Bonechi E, Ballerini C, Viola R - Sci Rep (2016)

Effects of different plant sRNA extracts on T cell proliferation.(a–d) T cells were exposed to DCs, in presence or not of FvmiR146, bolmiR874 or osamiR168 (10 ng/ml, (a), F. vesca total sRNA (b) or human and B. taurus total sRNA (10 ng/ml, (c) or sRNA fractions obtained as described in Material and Methods section (10 ng/ml, (d) or B. taurus total and 10–60 nt sRNA fraction (e), and LPS (10 ng/ml). Fractioning of sRNA has been performed by polyacrylamide electrophoresis separation. Panel (d) refers to the results obtained using 10–60 nt sRNA, 70–100 nt sRNA and 100–150 nt sRNA. After five days of T cells-DCs co-cultures, proliferation has been measured as [3H]-Thy uptake by liquid scintillation [3H]-Thy. MLR results are shown. Proliferation is presented as stimulation index, Percentage Stimulation above background is determined for each stimulated sample, through comparison with results from an unstimulated sample. Mean ± SD, N = 6, *p < 0.05, **p < 0.01, Kruskal Wallis, pretreatment (+miRNA duplexes or sRNA fractions) vs not-pretreated cells (none).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4863160&req=5

f4: Effects of different plant sRNA extracts on T cell proliferation.(a–d) T cells were exposed to DCs, in presence or not of FvmiR146, bolmiR874 or osamiR168 (10 ng/ml, (a), F. vesca total sRNA (b) or human and B. taurus total sRNA (10 ng/ml, (c) or sRNA fractions obtained as described in Material and Methods section (10 ng/ml, (d) or B. taurus total and 10–60 nt sRNA fraction (e), and LPS (10 ng/ml). Fractioning of sRNA has been performed by polyacrylamide electrophoresis separation. Panel (d) refers to the results obtained using 10–60 nt sRNA, 70–100 nt sRNA and 100–150 nt sRNA. After five days of T cells-DCs co-cultures, proliferation has been measured as [3H]-Thy uptake by liquid scintillation [3H]-Thy. MLR results are shown. Proliferation is presented as stimulation index, Percentage Stimulation above background is determined for each stimulated sample, through comparison with results from an unstimulated sample. Mean ± SD, N = 6, *p < 0.05, **p < 0.01, Kruskal Wallis, pretreatment (+miRNA duplexes or sRNA fractions) vs not-pretreated cells (none).
Mentions: Given that dsRNA binding to TLR3 is not sequence-dependent, we tested whether the anti-inflammatory efficacy shown by FvmiR168 could also be observed with other miRNAs such as FvmiR156, another abundant strawberry miRNA, bolmiR874 an abundant cabbage miRNA or osamiR168 from rice, the plant miRNA detected in blood plasma of human and animal subjects after dietary consumption of rice29. DCs treatment with synthetic equivalents of these plant miRNAs reduced T cell proliferation to a similar extent than FvmiR168 (Fig. 4a, p < 0.01).

Bottom Line: An increasing body of literature is addressing the immuno-modulating functions of miRNAs which include paracrine signaling via exosome-mediated intercellular miRNA.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.

View Article: PubMed Central - PubMed

Affiliation: Research 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.

No MeSH data available.


Related in: MedlinePlus