Inhibition of miR-99a-5p prevents allergen-driven airway exacerbations without compromising type-2 memory responses in the intestine following helminth infection.
Journal
Mucosal immunology
ISSN: 1935-3456
Titre abrégé: Mucosal Immunol
Pays: United States
ID NLM: 101299742
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
14
09
2020
accepted:
14
03
2021
revised:
16
02
2021
pubmed:
14
4
2021
medline:
28
12
2021
entrez:
13
4
2021
Statut:
ppublish
Résumé
Acute exacerbations (AE) of asthma, remain one of the biggest concerns for patients living with asthma. As such, identifying the causes, the molecular mechanisms involved and new therapeutic interventions to prevent AE is a high priority. Immunity to intestinal helminths involves the reactivation of type-2 immune responses leading to smooth muscle contraction and mucus hypersecretion-physiological processes very similar to acute exacerbations in the airways following allergen exposure. In this study, we employed a murine model of intestinal helminth infection, using Heligmosomoides polygyrus, to identify miRNAs during active expulsion, as a system for the identification of miRNAs that may contribute to AE in the airways. Concomitant with type-2 immunity and expulsion of H. polygyrus, we identified miR-99a-5p, miR-148a-3p and miR-155-5p that were differentially regulated. Systemic inhibition of these miRNAs, alone or in combination, had minimal impact on expulsion of H. polygyrus, but inhibition of miR-99a-5p or miR-155-5p significantly reduced house dust mite (HDM)-driven acute inflammation, modelling human acute exacerbations. Immunological, pathological and transcriptional analysis identified that miR-155-5p or miR-99a-5p contribute significantly to HDM-driven AE and that transient inhibition of these miRNAs may provide relief from allergen-driven AE, without compromising anti-helminth immunity in the gut.
Identifiants
pubmed: 33846533
doi: 10.1038/s41385-021-00401-x
pii: S1933-0219(22)00189-1
pmc: PMC8222002
doi:
Substances chimiques
Allergens
0
Biomarkers
0
MicroRNAs
0
Mirn99 microRNA, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
912-922Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Cancer Research UK
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UP_A253_1028
Pays : United Kingdom
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