miR103a-3p in extracellular vesicles from Fc?RI-aggregated human mast cells enhances IL-5 production by group 2 innate lymphoid cells - 05/05/21
Abstract |
Background |
Mast cells (MCs) are key regulators of IgE-mediated allergic inflammation. Cell-derived extracellular vesicles (EVs) contain bioactive compounds such as microRNAs. EVs can transfer signals to recipient cells, thus using a novel mechanism of cell-to-cell communication. However, whether MC-derived EVs are involved in FcεRI-mediated allergic inflammation is unclear.
Objective |
We sought to investigate the effect of EVs derived from FcεRI-aggregated human MCs on the function of human group 2 innate lymphoid cells (ILC2s).
Methods |
Human cultured MCs were sensitized with and without IgE for 1 hour and then incubated with anti-IgE antibody, IL-33, or medium alone for 24 hours. EVs in the MC supernatant were isolated by using ExoQuick-TC.
Results |
Coculture of ILC2s with EVs derived from the FcεRI-aggregated MCs significantly enhanced IL-5 production and sustained upregulation of IL-5 mRNA expression in IL-33–stimulated ILC2s, but IL-13 production and IL-13 mRNA expression were unchanged. miR103a-3p expression was upregulated in IL-33–stimulated ILC2s that had been cocultured with EVs derived from anti-IgE antibody–stimulated MCs. Transduction of an miR103a-3p mimic to ILC2s significantly enhanced IL-5 production by IL-33–stimulated ILC2s. miR103a-3p promoted demethylation of an arginine residue of GATA3 by downregulating protein arginine methyltransferase 5 (PRMT5) mRNA. Reduction of protein arginine methyltransferase 5 expression in ILC2s by using a small interfering RNA technique resulted in upregulation of IL-5 production by IL-33–stimulated ILC2s. Furthermore, the level of miR103a-3p expression was significantly higher in EVs from sera of patients with atopic dermatitis than in EVs from nonatopic healthy control subjects.
Conclusion |
Eosinophilic allergic inflammation may be exacerbated owing to ILC2 activation by MC-derived miR103a-3p.
Le texte complet de cet article est disponible en PDF.Key words : Extracellular vesicles, human mast cells, group 2 innate lymphoid cells, IL-5, miRNA103a-3p, methylated arginine residue, protein arginine methyltransferase 5
Abbreviations used : AD, EM, EV, ILC2, IMDM, MC, miRNA, NC, PGD2, PRMT, siRNA, Tg, 3'UTR
Plan
| Supported in part by a Grant-in-Aid for Early-Career Scientists (19K17687 [to S.T.]) and a Grant-in-Aid for Scientific Research from the MEXT of the Japanese Government (20K08811 [to Y.O.]), the Nihon University Research Grant for Social Implementation for 2020 (project No. Sya20-1201 [to Y.O.]), and the MEXT-Supported Program for the Strategic Research Foundation at Private Universities, 2015-2019 (project No. S1511014 [to Y.O., T.T., and Y.G.). |
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| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 147 - N° 5
P. 1878-1891 - mai 2021 Retour au numéro
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