Microbiota downregulates dendritic cell expression of miR-10a, which targets IL-12/IL-23p40

Xiaochang Xue, Ting Feng, Suxia Yao, Kyle J. Wolf, Chang Gong Liu, Xiuping Liu, Charles O. Elson, Yingzi Cong

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

Commensal flora plays important roles in the regulation of the gene expression involved in many intestinal functions and the maintenance of immune homeostasis, as well as in the pathogenesis of inflammatory bowel diseases. The microRNAs (miRNAs), a class of small, noncoding RNAs, act as key regulators in many biological processes. The miRNAs are highly conserved among species and appear to play important roles in both innate and adaptive immunity, as they can control the differentiation of various immune cells, as well as their functions. However, it is still largely unknown how microbiota regulates miRNA expression, thereby contributing to intestinal homeostasis and pathogenesis of inflammatory bowel disease. In our current study, we found that microbiota negatively regulated intestinal miR-10a expression, because the intestines, as well as intestinal epithelial cells and dendritic cells of specific pathogen-free mice, expressed much lower levels of miR-10a compared with those in germ-free mice. Commensal bacteria downregulated dendritic cell miR-10a expression via TLR-TLR ligand interactions through a MyD88- dependent pathway.We identified IL-12/IL-23p40, a key molecule for innate immune responses to commensal bacteria, as a target of miR-10a. The ectopic expression of the miR-10a precursor inhibited, whereas the miR-10a inhibitor promoted, the expression of IL-12/IL-23p40 in dendritic cells. Mice with colitis expressing higher levels of IL-12/IL-23p40 exhibited lower levels of intestinal miR-10a compared with control mice. Collectively, our data demonstrated that microbiota negatively regulates host miR-10a expression, which may contribute to the maintenance of intestinal homeostasis by targeting IL-12/IL-23p40 expression.

Original languageEnglish (US)
Pages (from-to)5879-5886
Number of pages8
JournalJournal of Immunology
Volume187
Issue number11
DOIs
StatePublished - Dec 1 2011

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Microbiota
Interleukin-12
Dendritic Cells
Down-Regulation
MicroRNAs
Homeostasis
Inflammatory Bowel Diseases
Innate Immunity
Maintenance
Bacteria
Biological Phenomena
Specific Pathogen-Free Organisms
Small Untranslated RNA
Gene Expression Regulation
Adaptive Immunity
Colitis
Intestines
Epithelial Cells
Ligands

ASJC Scopus subject areas

  • Immunology

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Microbiota downregulates dendritic cell expression of miR-10a, which targets IL-12/IL-23p40. / Xue, Xiaochang; Feng, Ting; Yao, Suxia; Wolf, Kyle J.; Liu, Chang Gong; Liu, Xiuping; Elson, Charles O.; Cong, Yingzi.

In: Journal of Immunology, Vol. 187, No. 11, 01.12.2011, p. 5879-5886.

Research output: Contribution to journalArticle

Xue, Xiaochang ; Feng, Ting ; Yao, Suxia ; Wolf, Kyle J. ; Liu, Chang Gong ; Liu, Xiuping ; Elson, Charles O. ; Cong, Yingzi. / Microbiota downregulates dendritic cell expression of miR-10a, which targets IL-12/IL-23p40. In: Journal of Immunology. 2011 ; Vol. 187, No. 11. pp. 5879-5886.
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