Trophoblast-Derived Exosomes Mediate Monocyte Recruitment and Differentiation

Introduction Trophoblast cells have been demonstrated to regulate monocyte migration and differentiation, leading to pro-inflammatory profiles. Because trophoblast cells release exosomes with immunoregulatory properties, trophoblast-derived exosomes are proposed to 'educate' monocytes, creating a pro-inflammatory environment. Method of study Exosomes were isolated from conditioned media of Swan71 cells by ultrafiltration and ultracentrifugation. Exosome-induced migration was assessed using a two-chamber system. Cytokine profiles were defined using cytokine arrays, and mRNA levels of affected cytokines were examined by qRT-PCR and ELISA. Results Within 20 min, 8-10% of monocytes took up labeled exosomes isolated from Swan71 cells. Trophoblast-derived exosomes increased monocyte migration in a dose-dependent manner and produced significant increases in production of interleukin (IL)-1 beta, IL-6, Serpin-E1, granulocyte colony-stimulating factor, granulocyte/monocyte colony-stimulating factor, and tumor necrosis factor-alpha. Conclusion This study presents the initial demonstration that trophoblast-derived exosomes are capable of recruiting and 'educating' monocytes to produce pro-inflammatory cytokine/chemokine profiles in a cell-contact-independent manner.