IL-33 Drives Inflammatory Changes and Extracellular Trap Formation in Eosinophils Involving Oxidised LDL and...

Area of Science:

• Immunology
• Cell Biology
• Molecular Medicine

Background:

• Elevated IL-33 levels are observed in eosinophilic airway diseases.
• IL-33 receptor expression is increased on eosinophils in type 2-high environments.
• The precise role of IL-33 in human eosinophil regulation is not fully understood.

Purpose of the Study:

• To investigate the inflammatory effects of IL-33 on human eosinophil cellular functions.
• To elucidate the molecular mechanisms underlying IL-33-mediated eosinophil activation.

Main Methods:

• Human blood eosinophils were stimulated with IL-33, TNF-α, oxidised low-density lipoprotein (oxLDL), and complement fragments (C3a, C5a).
• Multi-omics analyses (transcriptomics, proteomics) were employed.
• Extracellular trap formation (ETosis) was assessed using SYTOX staining and microscopy.

Main Results:

• IL-33 and TNF-α induced a distinct inflammatory gene signature, upregulating cell surface markers and inflammatory mediators.
• CD22 upregulation was specifically linked to IL-33 stimulation.
• IL-33 triggered ETosis through NADPH oxidase, MAPK, and PI3K pathways, while oxLDL and complement fragments influenced eosinophil survival and adhesion molecule expression.

Conclusions:

• IL-33, oxLDL, and the complement cascade synergistically induce inflammatory changes in eosinophils, fostering an ETosis-prone phenotype.
• These inflammatory pathways represent promising therapeutic targets for refractory eosinophilic diseases.