RANKL is necessary and sufficient to initiate development of antigen-sampling M cells in the intestinal epithelium

Area of Science:

• Immunology
• Gastroenterology
• Cell Biology

Background:

• Microfold cells (M cells) are specialized epithelial cells in organized mucosal lymphoid tissues.
• M cells transport antigens, including commensal bacteria, to antigen-presenting cells (APCs).
• Receptor activator of NF-kappaB ligand (RANKL) is expressed by stromal cells in Peyer's patches (PP).

Purpose of the Study:

• To investigate the role of RANKL in the development and function of M cells.
• To determine if RANKL is sufficient to induce M cell differentiation.

Main Methods:

• Analysis of RANKL null mice for M cell populations and antigen uptake.
• Administration of antibodies to neutralize RANKL in wild-type mice.
• Systemic administration of exogenous RANKL to assess M cell induction.

Main Results:

• RANKL null mice exhibited a severe deficiency (<2%) in Peyer's patch M cells and reduced bead uptake.
• RANKL neutralization in adult mice eliminated most PP M cells.
• Exogenous RANKL administration restored M cells in RANKL null mice and induced villous M cells with antigen uptake capacity.

Conclusions:

• RANKL availability is the critical factor controlling M cell differentiation from RANK-expressing intestinal epithelial precursor cells.
• RANKL plays a key role in both the development and function of M cells throughout the small intestine.