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2016 ; 11
(3
): e0150379
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Epithelium-Intrinsic MicroRNAs Contribute to Mucosal Immune Homeostasis by
Promoting M-Cell Maturation
#MMPMID26930511
Nakato G
; Hase K
; Sato T
; Kimura S
; Sakakibara S
; Sugiyama M
; Obata Y
; Hanazato M
; Iwanaga T
; Ohno H
PLoS One
2016[]; 11
(3
): e0150379
PMID26930511
show ga
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 (Dicer?IEC) and analyzed
intestinal phenotypes, including M-cell differentiation, morphology and function.
Dicer?IEC 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 Dicer?IEC mice. These results suggest that
miRNAs play a significant role in M cell differentiation and help secure mucosal
immune homeostasis.
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