Peyer's patch dendritic cells sample antigens by extending dendrites through M cell-specific transcellular pores

Area of Science:

• Immunology
• Gastroenterology
• Cell Biology

Background:

• Peyer's patches (PPs) are crucial inductive sites for mucosal immunity in the small intestine.
• Specialized M cells in PPs transport luminal antigens to subepithelial dome (SED) resident dendritic cells (DCs).
• Some SED DCs, termed lysozyme-high DCs (LysoDCs), exhibit potent phagocytic activity.

Purpose of the Study:

• To investigate the in vivo mechanisms by which LysoDCs capture luminal antigens within Peyer's patches.
• To elucidate the interaction between M cells and LysoDCs during antigen sampling.

Main Methods:

• Utilized 2-photon microscopy on explants from lys-EGFP reporter mice for real-time LysoDC visualization.
• Observed LysoDC behavior and interactions within the Peyer's patch microenvironment.

Main Results:

• LysoDCs extend dendrites through M-cell transcellular pores into the gut lumen.
• M-cell adhesion molecules (JAM-A, EpCAM) are recruited to these transcellular migration sites.
• Transcellular dendrites actively sample luminal contents, including bacteria and particles, before retracting.

Conclusions:

• A novel antigen sampling mechanism involving M cell-DC cooperation in PPs is described.
• This M cell-DC interaction facilitates direct capture of luminal antigens by LysoDCs.
• The identified mechanism offers potential for targeted mucosal vaccine strategies.