miR103a-3p in extracellular vesicles from FcεRI-aggregated human mast cells enhances IL-5 production by group 2 innate lymphoid cells.
J Allergy Clin Immunol
; 147(5): 1878-1891, 2021 05.
Article
em En
| MEDLINE
| ID: mdl-33465368
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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos
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Citocinas
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Receptores de IgE
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MicroRNAs
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Vesículas Extracelulares
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Mastócitos
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article