"Tolerosomes" are produced by intestinal epithelial cells.

Area of Science:

• Immunology
• Gastroenterology
• Cell Biology

Background:

• Oral administration of antigens is crucial for inducing specific immune tolerance.
• The intestinal epithelium plays a key role in sampling, processing, and transporting gut antigens.
• Mechanisms by which oral antigens induce tolerance are not fully understood.

Purpose of the Study:

• To describe a novel supra-molecular structure, the

Main Methods:

• Isolation of vesicular structures from intestinal epithelial cells and serum.
• Characterization of the vesicular structure size and molecular cargo.
• Assessment of the tolerogenic capacity of isolated vesicles in vivo.
• Functional assays involving ultracentrifugation and antibody-mediated depletion of MHC class II.

Main Results:

• A novel, approximately 40 nm vesicular structure, termed "tolerosome", was identified.
• Tolerosomes are released from small intestinal epithelial cells and carry MHC class II molecules with bound antigenic peptides.
• Isolated tolerosomes effectively induced antigen-specific tolerance in naive recipient animals.
• Tolerance induction was abrogated upon removal of tolerosomes or MHC class II molecules.

Conclusions:

• Tolerosomes are key mediators of oral antigen sampling and presentation.
• These structures efficiently induce antigen-specific immune tolerance via MHC class II presentation.
• Tolerosomes represent a novel mechanism for maintaining gut homeostasis and preventing unwanted immune responses to dietary antigens.