Epithelium-intrinsic MicroRNAs contribute to mucosal immune homeostasis by promoting M-cell maturation

Gaku Nakato, Koji Hase, Takao Sato, Shunsuke Kimura, Sayuri Sakakibara, Machiko Sugiyama, Yuuki Obata, Misaho Hanazato, Toshihiko Iwanaga, Hiroshi Ohno

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Article numbere0150379
JournalPloS one
Volume11
Issue number3
DOIs
Publication statusPublished - 2016 Mar

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Nakato, G., Hase, K., Sato, T., Kimura, S., Sakakibara, S., Sugiyama, M., Obata, Y., Hanazato, M., Iwanaga, T., & Ohno, H. (2016). Epithelium-intrinsic MicroRNAs contribute to mucosal immune homeostasis by promoting M-cell maturation. PloS one, 11(3), [e0150379]. https://doi.org/10.1371/journal.pone.0150379