Multivesicular bodies in intestinal epithelial cells: responsible for MHC class II-restricted antigen processing and origin of exosomes.

Immunology
Jürgen BüningAndreas Gebert

Abstract

In normal conditions intestinal epithelial cells (IECs) constitutively stimulate regulatory CD4(+) T cells. However, in Crohn's disease (CD), this major histocompatibility complex (MHC) class II-restricted antigen presentation results in stimulation of proinflammatory CD4(+) T cells. We hypothesized that these alternative functions might be mediated by differential sorting and processing of antigens into distinct MHC II-enriched compartments (MIICs). Accordingly, we analysed the endocytic pathways of lumenally applied ovalbumin (OVA) in IECs of the jejunum and ileum of wild-type (WT) and TNFDeltaARE/WT mice that develop a CD-resembling ileitis. Using quantitative reverse transcription polymerase chain reaction, we found that messenger RNA levels of interferon-gamma, tumour necrosis factor-alpha, interleukin-17 and interleukin-10 were significantly up-regulated in the inflamed ileum of TNFDeltaARE/WT mice, confirming CD-like inflammation. Fluorescence and immunoelectron microscopy revealed the presence of MHC II and invariant chain throughout the late endocytic compartments, with most molecules concentrated in the multivesicular bodies (MVB). OVA was targeted into MVB and, in contrast to other MIICs, accumulated in these structu...Continue Reading

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Citations

Jul 21, 2010·Inflammatory Bowel Diseases·Paul HendersonDavid C Wilson
Jul 24, 2012·Advanced Drug Delivery Reviews·Aaron TanAlexander M Seifalian
Jun 18, 2014·Pathophysiology : the Official Journal of the International Society for Pathophysiology·Yava L Jones-Hall, Matthew B Grisham
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Oct 26, 2018·Proceedings of the National Academy of Sciences of the United States of America·Do-Kyun KimDean D Metcalfe
Feb 23, 2019·Cellular & Molecular Immunology·Hongdi MaShu Zhu

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