TITLE

Intestinal epithelial exosomes carry MHC class II/peptides able to inform the immune ststem in mice

AUTHOR(S)
van Niel, G.; Mallegol, J.; Bevilacquea, C.; Candalh, C.; Brugière, S.; Tomaskovic-Crook, E.; Heath, J. K.; Cerf-Bensussan, N.; Heyman, M.
PUB. DATE
December 2003
SOURCE
Gut;Dec2003, Vol. 52 Issue 12, p1690
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Intestinal epithelial cells secrete exosome-like vesicles. The aim of this study was to characterise murine intestinal epithelial exosomes and to analyse their capacity to inform the immune system in vivo in mice. Methods: Epithelial exosomes were obtained from the murine epithelial cell line MODE K incubated in the presence or absence of interferon γ (IFN--γ) together with pepsin/trypsin ovalbumin hydrolysate (hOVA) to mimic luminal digestion. Exosomes isolated from MODE K conditioned media (EXO-hOVA and EXO- hOVA-IFN) were characterised by western blot, peptide mapping, and mass spectrometry. They were injected intraperitoneally to C3H/HeN mice to test their immunocompetence. Results: MODE K epithelial exosomes displayed major histocompatibility complex (MHC) class I and class II (upregulated by IFN-γ) molecules and tetraspan proteins (CD9, CDB1, CD82) potentially involved in the binding to target cells. A33 antigen, an Ig-like molecule highly specific for intestinal epithelial cells, was enriched in exosomes and was also found in mice mesenteric lymph nodes, suggesting exosome migration towards the gut associated lymphoid tissues. Intraperitoneal injection of EXO-hOVA or EXO-hOVA-IFN did not induce humoral or cellular tolerance to OVA in mice. In contrast, exosomes obtained after incubation with IFN-γ (EXO-hOVA-IFN), bearing abundant MHC class Il/OVA complexes, induced a specific humoral immune response. Conclusions: Epithelial exosomes are antigen presenting vesicles bearing MHC class Il/peptide complexes that prime for an immunogenic rather than tolerogenic response in the context of a systemic challenge. In the intestine, both the mucosal microenvironment and local effector cells are probably key players in determining the outcome of the immune response to exosome derived epitopes.
ACCESSION #
12940905

 

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