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

• Authors: Kathryn A. Knoop, Emory University; Nachiket Kumar, Emory University; Betsy R. Butler, Emory University; Senthilkumar K. Sakthivel, Emory University; Rebekah T. Taylor, Emory University; Tomonori Nochi, University of Tokyo; Hisaya Akiba, Juntendo University; Hideo Yagita, Juntendo University; Hiroshi Kiyono, University of Tokyo; Ifor Williams, Emory University
• Journal Title: Journal of Immunology
• Volume: Volume 183, Number 9
• Publisher: American Association of Immunologists | 2009-11-01, Pages 5738-5747
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.4049/jimmunol.0901563
• Subjects: Health Sciences, Pathology; Health Sciences, Immunology

Abstract

Microfold cells (M cells) are specialized epithelial cells situated over Peyer’s patches (PP) and other organized mucosal lymphoid tissues that transport commensal bacteria and other particulate antigens into intraepithelial pockets accessed by antigen-presenting cells. The TNF superfamily member RANKL is selectively expressed by subepithelial stromal cells in PP domes. We found that RANKL null mice have less than 2% of wild type levels of PP M cells and markedly diminished uptake of 200 nm diameter fluorescent beads. Antibody-mediated neutralization of RANKL in adult wild type mice also eliminated most PP M cells. The M cell deficit in RANKL null mice was corrected by systemic administration of exogenous RANKL. Treatment with RANKL also induced the differentiation of villous M cells on all small intestinal villi with the capacity for avid uptake of Salmonella and Yersinia organisms and fluorescent beads. The RANK receptor for RANKL is expressed by epithelial cells throughout the small intestine. We conclude that availability of RANKL is the critical factor controlling the differentiation of M cells from RANK-expressing intestinal epithelial precursor cells.