Plasma-derived exosomes in chronic spontaneous urticaria induce the release of inflammatory mediators from mast cell...

The excessive release of inflammatory mediators in mast cells is considered a core link in the progression of Chronic spontaneous Urticaria (CSU). Exosomes are nanosized membrane-bound fluid vesicles in the body that can induce immune dysfunction and impact disease progression. This study aims to explore the critical role of exosomes derived from plasma of patients in the progression of CSU.

Transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and protein blot were used to characterize the exosomes. Bioinformatics analysis was used to obtain the differential expression of miRNAs between CSU plasma exosomes (CSU-Exos) and healthy volunteers exosomes (Nor-Exos). The molecular mechanisms were explored by using ELISA, RT-qPCR, western blot, and immunofluorescence staining.

Exosomes were isolated from the plasma of CSU patients and healthy volunteers. The CSU-Exos stimulated the release of inflammatory mediators in human mast cells (HMC-1). In addition, miRNA-619-5p was significantly upregulated in CSU-Exos. Functional experiments demonstrated that overexpression of miRNA-619-5p enhanced the release of inflammatory mediators in HMC-1 cells by targeting and inhibiting suppressor of cytokine signaling 4 (SOCS4), whereas knockdown of miRNA-619-5p reversed these effects. Furthermore, SOCS4 overexpression attenuated the pro-inflammatory effects induced by miRNA-619-5p, while SOCS4 knockdown further exacerbated the inflammatory response.

Derived from the CSU plasma exosomal miRNA-619-5p, it promoted the release of inflammatory mediators in mast cells by regulating SOCS4.