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

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Title: RANKL regulates differentiation of microfold cells in mouse nasopharynx-associated lymphoid tissue (NALT)
Authors: Mutoh, Mami Browse this author
Kimura, Shunsuke Browse this author →KAKEN DB
Takahashi-Iwanaga, Hiromi Browse this author →KAKEN DB
Hisamoto, Meri Browse this author
Iwanaga, Toshihiko Browse this author →KAKEN DB
Iida, Junichiro Browse this author →KAKEN DB
Keywords: Microfold cells (M cells)
Follicle-associated epithelium
Nasopharynx-associated lymphoid tissue (NALT)
Glycoprotein 2 (GP2)
Receptor activator of nuclear factor kappa-B ligand (RANKL)
Issue Date: Apr-2016
Publisher: Springer
Journal Title: Cell and Tissue Research
Volume: 364
Issue: 1
Start Page: 175
End Page: 184
Publisher DOI: 10.1007/s00441-015-2309-2
PMID: 26553655
Abstract: 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.
Rights: The final publication is available at
Type: article (author version)
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 木村 俊介

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