Reduced miR-146a-5p Is a Biomarker of Infant Respiratory Diseases Contributing to Immune Dysregulation in Small Airway Epithelial Cells

• Published in: Cells (Basel, Switzerland) Vol. 11; no. 17; p. 2746
• Main Authors: Rodrigo-Muñoz, José M, Gil-Martínez, Marta, Lorente-Sorolla, Clara, Sastre, Beatriz, García-García, María Luz, Calvo, Cristina, Casas, Inmaculada, del Pozo, Victoria
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.09.2022; MDPI
• Subjects: Age; Airway (Medicine); Asthma; Babies; Biological markers; Biomarkers; Bronchopneumonia; Children; Diagnosis; Diseases; Dyspnea; Epigenetics; Epithelial cells; Gene expression; Gene regulation; Genetic aspects; Health aspects; immune regulation; Immune response; infant respiratory diseases; Infants; Infections; Influenza; MicroRNA; MicroRNAs; miRNA; Pediatric research; Post-transcription; Questionnaires; Respiratory diseases; Respiratory syncytial virus; Respiratory tract; Respiratory tract diseases; Thymic stromal lymphopoietin; Viral infections; Viruses; Wheezing; Spain; Basel Switzerland; United States > US; Madrid Spain; Switzerland; Germany
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11172746

Respiratory diseases such as bronchiolitis, and those with wheezing episodes, are highly important during infancy due to their potential chronicity. Immune response dysregulation is critical in perpetuating lung damage. Epigenetic modifications including microRNA (miRNA) post-transcriptional regulation are among the factors involved in alleviating inflammation. We evaluated the expression of miR-146a-5p, a previously described negative regulator of immunity, in infants with respiratory diseases, in order to study epigenetic regulation of the immune response. Nasopharyngeal aspirate (NPA) was obtained from infants with bronchiolitis (ongoing and post-disease) or with wheezing episodes in addition to healthy controls. Virus presence was determined by nested PCR, while miRNA and gene expression were studied in cells from NPAs using qPCR. Healthy small airway epithelial cells (SAECs) were used as an in vitro model. We observe a reduction in miR-146a-5p expression in infants with either of the two diseases compared to controls, suggesting the potential of this miRNA as a disease biomarker. Post-bronchiolitis, miR-146a-5p expression increases, though without reaching levels of healthy controls. MiR-146a-5p expression correlates inversely with the immune-related gene PTGS2, while its expression correlates directly with TSLP. When heathy donor SAECs are stimulated by poly:IC, we observe an increase in miR-146a-5p, with wounds having a synergistic effect. In conclusion, infants with respiratory diseases present reduced miR-146a-5p expression, possibly affecting immune dysregulation.