Immune-regulatory microRNA expression levels within circulating extracellular vesicles correspond with the appearance of local symptoms after seasonal flu vaccination

PLoS One. 2019 Jul 9;14(7):e0219510. doi: 10.1371/journal.pone.0219510. eCollection 2019.

Abstract

Extracellular vesicles (EVs) contain microRNAs (miRNAs) that regulate the innate immune responses, such as the production of pro-inflammatory cytokines. The excessive production of pro-inflammatory cytokines after vaccination can cause local adverse reactions, such as pain, itching, swelling, and redness. Previous studies have shown that circulating EV miR-451a regulates innate immune responses, and miR-451a levels in serum EVs are negatively correlated with the pro-inflammatory cytokine expression levels in response to the influenza vaccine. Since excessive pro-inflammatory cytokine production is a cause of the local adverse reactions to vaccination, we investigated whether miR-451a levels in serum EVs correlate with local symptoms at the vaccination site, such as pain, itching, swelling, and redness. Interestingly, miR-451a levels in serum EVs were inversely correlated with the number of symptoms after vaccination. We determined the level of several other immune-regulatory miRNAs in serum EVs. Using the immune-regulatory miRNA levels of miR-22, miR-29a, miR-451a, and miR-107, we calculated a normalized miRNA level for each healthy donor and found that the normalized miRNA levels were significantly correlated with the number of local symptoms after vaccination. Our data indicated that immune-regulatory miRNA levels in serum EVs can be used as biomarkers to assess local symptoms after influenza vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers
  • Extracellular Vesicles* / genetics
  • Female
  • Humans
  • Immunomodulation*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology
  • Influenza, Human / diagnosis
  • Influenza, Human / genetics*
  • Influenza, Human / immunology*
  • Influenza, Human / prevention & control
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Seasons
  • Symptom Assessment
  • Vaccination
  • Young Adult

Substances

  • Biomarkers
  • Influenza Vaccines
  • MicroRNAs

Grants and funding

This work was funded by the Japan Agency for Medical Research and Development (AMED), the Ministry of Education, Science, and Technology (MEXT), PRESTO JST, the Waksman Foundation of Japan, the Shinnihon Foundation of Advanced Medical Treatment Research, the Naito Foundation, the Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Care, and the Cosmetology Research Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.