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

Kathryn A. Knoop, Nachiket Kumar, Betsy R. Butler, Senthilkumar K. Sakthivel, Rebekah T. Taylor, Tomonori Nochi, Hisaya Akiba, Hideo Yagita, Hiroshi Kiyono, Ifor R. Williams

Research output: Contribution to journalArticlepeer-review

214 Citations (Scopus)


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 Ags into intraepithelial pockets accessed by APCs. The TNF superfamily member receptor activator of NF-κB ligand (RANKL) is selectively expressed by subepithelial stromal cells in PP domes. We found that RANKL null mice have <2% of wild-type levels of PP M cells and markedly diminished uptake of 200 nm diameter fluorescent beads. Ab-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 villousMcells 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.

Original languageEnglish
Pages (from-to)5738-5747
Number of pages10
JournalJournal of Immunology
Issue number9
Publication statusPublished - 2009 Nov 1
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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