Inhibition of miR-99a-5p prevents allergen-driven airway exacerbations without compromising type-2 memory responses in the intestine following helminth infection
| Autor: | Eleni Amaniti, Nikolay Nikolov, Stephanie Czieso, Cary D. Austin, Abdul Sesay, Sean Flanagan, Dennis Wilson, Christine Clarke, Jessica Mills, Riccardo Guidi, Yi Cao, Mark S. Wilson, Probir Chakravaty, Alison Huynh, Lewis J. Entwistle, Shannon Hambro, Helena Aegerter, Laurie Leong, Victor Nunez, Angela Martzall |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Immunology Inflammation medicine.disease_cause Article Host-Parasite Interactions Mice 03 medical and health sciences 0302 clinical medicine Immune system Allergen Immunity parasitic diseases Medicine and Health Sciences medicine Animals Immunology and Allergy Asthma House dust mite biology business.industry Gene Expression Profiling Smooth muscle contraction Allergens medicine.disease biology.organism_classification Immunity Innate MicroRNAs 030104 developmental biology Disease Progression Disease Susceptibility Heligmosomoides polygyrus Helminthiasis Animal medicine.symptom business Immunologic Memory Biomarkers 030215 immunology |
| Zdroj: | MUCOSAL IMMUNOLOGY Mucosal Immunology |
| ISSN: | 1933-0219 1935-3456 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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