Exosomes from the Uterine Cavity Mediate Immune Dysregulation via Inhibiting the JNK Signal Pathway in Endometriosis

Abstract

Endometriosis is a chronic inflammatory disease with an uncertain pathogenesis. Peritoneal immune dysregulation plays an important role in the pathogenesis of endometriosis. Exosomes are messengers of intercellular communication. This study mainly investigated the role of exosomes from the uterine cavity in endometriosis. Exosomes of the uterine aspirate fluid were isolated and cocultured with macrophages for 48 h. Flow cytometry was used to detect macrophage polarization. A Human MAPK Phosphorylation Antibody Array and Western blot were used to detect the phosphorylation of the MAPK pathway. A microRNA sequencing analysis was used to detect differentially expressed miRNAs. Our research found that exosomes of the uterine aspirate fluid from endometriosis could reduce the proportion of CD80+ macrophages. Additionally, it could inhibit the expression of P-JNK in macrophages. However, the JNK activator anisomycin could increase the proportion of CD80+ macrophages. In addition, exosomes of the uterine aspirate fluid from endometriosis could promote the migration and invasion of endometrial stromal cells by acting on macrophages. The expression of miR-210-3p was increased in both exosomes and the eutopic endometrium in patients with endometriosis through miRNA sequencing, which could also reduce the proportion of CD80+ macrophages. In summary, we propose that exosomes from the uterine cavity in patients with endometriosis may affect the phenotype of macrophages by inhibiting the JNK signaling pathway, thus mediating the formation of an immunological microenvironment conducive to the development of endometriosis.

Keywords

• exosomes
• uterine aspirate fluid
• microRNAs
• macrophages polarization
• immune dysregulation
• endometriosis