title: Epithelium-Intrinsic MicroRNAs Contribute to Mucosal Immune Homeostasis by Promoting M-Cell Maturation.
abstract: M cells in the follicle-associated epithelium (FAE) of Peyer's patches (PPs) serve as a main portal for external antigens and function as a sentinel in mucosal immune responses. The scarcity of these cells has hampered identification of M cell-specific molecules. Recent efforts have begun to provide insight into antigen transcytosis and differentiation of M cells; however, the molecular mechanisms underlying these processes are not fully elucidated. Small non-coding RNAs including microRNA (miRNA) have been reported to regulate gene expression and control various biological processes such as cellular differentiation and function. To evaluate the expression of miRNAs in FAE, including M cells, we previously performed microarray analysis comparing intestinal villous epithelium (VE) and PP FAE. Here we confirmed FAE specific miRNA expression levels by quantitative PCR. To gain insight into miRNA function, we generated mice with intestinal epithelial cell-specific deletion of Dicer1 (DicerΔIEC) and analyzed intestinal phenotypes, including M-cell differentiation, morphology and function. DicerΔIEC mice had a marked decrease in M cells compared to control floxed Dicer mice, suggesting an essential role of miRNAs in maturation of these cells. Furthermore, transmission electron microscopic analysis revealed that depletion of miRNA caused the loss of endosomal structures in M cells. In addition, antigen uptake by M cells was impaired in DicerΔIEC mice. These results suggest that miRNAs play a significant role in M cell differentiation and help secure mucosal immune homeostasis.
authors.affiliation: Laboratory for Intestinal Ecosystem, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Kanagawa, Japan.|Laboratory for Immunobiology, Graduate School of Medical Life Science, Yokohama City University, Kanagawa, Japan.
authors.forename: Gaku
authors.initials: G
authors.lastname: Nakato
authors.affiliation: Laboratory for Intestinal Ecosystem, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Kanagawa, Japan.|Division of Mucosal Barriology, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.|PRESTO, Japan Science and Technology Agency, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Hase
authors.affiliation: Laboratory for Intestinal Ecosystem, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Kanagawa, Japan.|Laboratory for Immunobiology, Graduate School of Medical Life Science, Yokohama City University, Kanagawa, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Sato
authors.affiliation: Laboratory of Histology and Cytology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kimura
authors.affiliation: Laboratory for Intestinal Ecosystem, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Kanagawa, Japan.
authors.forename: Sayuri
authors.initials: S
authors.lastname: Sakakibara
authors.affiliation: Laboratory for Immunobiology, Graduate School of Medical Life Science, Yokohama City University, Kanagawa, Japan.
authors.forename: Machiko
authors.initials: M
authors.lastname: Sugiyama
authors.affiliation: Laboratory for Intestinal Ecosystem, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Kanagawa, Japan.|Division of Mucosal Barriology, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.|Graduate School of Medical and Pharmaceutical Sciences, Chiba University, Chiba, Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Obata
authors.affiliation: Laboratory for Intestinal Ecosystem, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Kanagawa, Japan.|Laboratory for Immunobiology, Graduate School of Medical Life Science, Yokohama City University, Kanagawa, Japan.
authors.forename: Misaho
authors.initials: M
authors.lastname: Hanazato
authors.affiliation: Laboratory of Histology and Cytology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Iwanaga
authors.affiliation: Laboratory for Intestinal Ecosystem, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Kanagawa, Japan.|Laboratory for Immunobiology, Graduate School of Medical Life Science, Yokohama City University, Kanagawa, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohno
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006706:Homeostasis / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000276:immunology*; D057900:Transcytosis / Q000276:immunology
chemical_list: D035683:MicroRNAs