• Country: TAIWAN
  • Official Title: 研究員
  • Department: 臺中榮民總醫院 醫學研究部

Speech Title

The Pathogenic Mechanisms of Extracellular Vesicles in Human Disease
胞外小體在人類疾病的致病機轉

Neutrophil extracellular traps (NETs) are released by neutrophils to capture microbes and modulate inflammation. Accumulating evidence showed that hyperactive NETs formation that can trigger uncontrolled immunothrombosis and play a crucial role in the pathogenesis of many diseases. Extracellular vesicles (EVs) are vehicles which carry cellular components to contribute intercellular communication, we explored the roles of EVs in NETs formation. We demonstrated that miR‑223 inhibits NETs formation through regulating calcium influx and EVs transmission. We identified that down-regulation of miR-223 in neutrophils elicited NET formation to promote the inflammatory response in atopic dermatitis. A drop in circulating level of miR-223 carried by neutrophil-derived EVs increased keratinocytes secretion of CCL17 and TSLP, potentially contributing to the skin pathology. On the other hand, we observed that the SARS-CoV-2 spike protein activated platelets directly, followed by the subsequent intracellular miR-21 upregulation and then were loaded into platelet-derived EVs (pEVs). The pEVs-carried miR-21 interacted with TLR7/8 to prime p47phox phosphorylation in neutrophils, resulting in NADPH oxidase activation to promote ROS production and NETs enhancement. The levels of miR-223/miR-21 were correlated with NETs formation; their mimic or inhibitor could efficiently suppress NETs formation/hyperactivation, which may become potential therapeutic targets.