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Exosome secretion of dendritic cells is regulated by Hrs, an ESCRT-0 protein

2010; Elsevier BV; Volume: 399; Issue: 3 Linguagem: Inglês

10.1016/j.bbrc.2010.07.083

1090-2104

Keiichi Tamai, Nobuyuki Tanaka, Takashi Nakano, Eiji Kakazu, Yasuteru Kondo, Jun Inoue, Masaaki Shiina, Koji Fukushima, Tomoaki Hoshino, Kouichi Sano, Yoshiyuki Ueno, Tooru Shimosegawa, Kazuo Sugamura,

Immunotherapy and Immune Responses

Exosomes are nanovesicles derived from multivesicular bodies (MVBs) in antigen-presenting cells. The components of the ESCRT (endosomal sorting complex required for transport) pathway are critical for the formation of MVBs, however the relationship between the ESCRT pathway and the secretion of exosomes remains unclear. We here demonstrate that Hrs, an ESCRT-0 protein, is required for fascilitating the secretion of exosomes in dendritic cells (DCs). Ultrastructural analyses showed typical saucer-shaped exosomes in the culture supernatant from both the control and Hrs-depleted DCs. However, the amount of exosome secretion was significantly decreased in Hrs-depleted DCs following stimulations with ovalbumin (OVA) as well as calcium ionophore. Antigen-presentation activity was also suppressed in exsosomes purified from Hrs-depleted DCs, while no alteration in OVA degradation was seen in Hrs-depleted DCs. These data indicated that Hrs is involved in the regulation of antigen-presentation activity through the exosome secretion.