title: RANKL regulates differentiation of microfold cells in mouse nasopharynx-associated lymphoid tissue (NALT).
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.
authors.affiliation: Department of Orthodontics, Hokkaido University Graduate School of Dental Medicine, Sapporo, 060-8586, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Mutoh
authors.affiliation: Laboratory of Histology and Cytology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, 060-8638, Japan. skimu@med.hokudai.ac.jp.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kimura
authors.affiliation: Laboratory of Histology and Cytology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Takahashi-Iwanaga
authors.affiliation: Division of Oral Functional Prosthodontics, Department of Oral Pathobiological Science, Hokkaido University Graduate School of Dental Medicine, Sapporo, 060-8586, Japan.
authors.forename: Meri
authors.initials: M
authors.lastname: Hisamoto
authors.affiliation: Laboratory of Histology and Cytology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Iwanaga
authors.affiliation: Department of Orthodontics, Hokkaido University Graduate School of Dental Medicine, Sapporo, 060-8586, Japan.
authors.forename: Junichiro
authors.initials: J
authors.lastname: Iida
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D058851:GPI-Linked Proteins / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010614:Pharynx / Q000166:cytology / Q000276:immunology*; D053245:RANK Ligand / Q000276:immunology / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology
chemical_list: D000943:Antigens, Differentiation; D058851:GPI-Linked Proteins; C495998:Gp2 protein, mouse; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse
keywords: Follicle-associated epithelium; Glycoprotein 2 (GP2); Microfold cells (M cells); Nasopharynx-associated lymphoid tissue (NALT); Receptor activator of nuclear factor kappa-B ligand (RANKL)