title: Exosome secretion of dendritic cells is regulated by Hrs, an ESCRT-0 protein.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tamai
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
authors.forename: Eiji
authors.initials: E
authors.lastname: Kakazu
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Kondo
authors.forename: Jun
authors.initials: J
authors.lastname: Inoue
authors.forename: Masaaki
authors.initials: M
authors.lastname: Shiina
authors.forename: Koji
authors.initials: K
authors.lastname: Fukushima
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hoshino
authors.forename: Kouichi
authors.initials: K
authors.lastname: Sano
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ueno
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sugamura
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology*; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D055354:Exosomes / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D010750:Phosphoproteins; C096164:hepatocyte growth factor-regulated tyrosine kinase substrate; D010047:Ovalbumin