RANKL regulates differentiation of microfold cells in mouse nasopharynx-associated lymphoid tissue (NALT)

Mami Mutoh, Shunsuke Kimura, Hiromi Takahashi-Iwanaga, Meri Hisamoto, Toshihiko Iwanaga, Junichiro Iida

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)


Murine nasopharynx-associated lymphoid tissue (NALT), located at the base of the nasal cavity, serves as a major site for the induction of mucosal immune responses against airway antigens. The follicle-associated epithelium (FAE) covering the luminal surface of NALT is characterized by the presence of microfold cells (M cells), which take up and transport luminal antigens to lymphocytes. Glycoprotein 2 (GP2) has recently been identified as a reliable marker for M cells in Peyer’s patches of the intestine. However, the expression of GP2 and other functional molecules in the M cells of NALT has not yet been examined. We have immunohistochemically detected GP2-expressing cells in the FAE of NALT and the simultaneous expression of other intestinal M-cell markers, namely Tnfaip2, CCL9, and Spi-B. These cells have been further identified as M cells because of their higher uptake capacity of luminal microbeads. Electron microscopic observations have shown that GP2-expressing cells on the FAE display morphological features typical of M cells: they possess short microvilli and microfolds on the luminal surface and are closely associated with intraepithelial lymphocytes. We have also found that the receptor activator of nuclear factor kappa-B ligand (RANKL) is expressed by stromal cells underneath the FAE, which provides its receptor RANK. The administration of RANKL markedly increases the number of GP2+Tnfaip2+ cells on the NALT FAE and that of intestinal M cells. These results suggest that GP2+Tnfaip2+ cells in NALT are equivalent to intestinal M cells, and that RANKL-RANK signaling induces their differentiation.

Original languageEnglish
Pages (from-to)175-184
Number of pages10
JournalCell and Tissue Research
Issue number1
Publication statusPublished - 2016 Apr 1
Externally publishedYes


  • Follicle-associated epithelium
  • Glycoprotein 2 (GP2)
  • Microfold cells (M cells)
  • Nasopharynx-associated lymphoid tissue (NALT)
  • Receptor activator of nuclear factor kappa-B ligand (RANKL)

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology


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