Transcriptomics

Dataset Information

39

Helicobacter pylori induce miR-155 in T cells in a cAMP-Foxp3 dependant manner


ABSTRACT: The human pathogen Helicobacter pylori (Hp) colonizes the gastric epithelium as a unique niche in the stomach. Infections commonly occur in childhood and persist lifelong, leading in some cases to adenocarcinoma and MALT lymphoma. Several studies define mammalian microRNAs as key regulators of the immune system and of carcinogenesis processes. Here, we show Hp infection induces miR-155 expression in epithelial and hematopoietic cells in vitro and in vivo. This induction is mediated by at least two main bacterial virulence factors, the vacuolating toxin (VacA) and the gamma-glutamyl transpeptidase (GGT) in an LPS independent manner. Using adenylate cyclases agonists and inhibitor, we demonstrated that the miR-155 microRNA regulatory cascade in Hp infection involves the second messenger cyclic adenosine monophosphate (cAMP). Furthermore, the study showed that a knock-down of the Foxp3 transcription factor in T cells abolishes miR-155 expression. Together, these findings are the first demonstration of a direct interconnection between the regulatory T cell development factor Foxp3 and a microRNA. This study supports the link between Hp infection, regulation of cellular immunity, inflammation and cancer development. A color-swap dye reversal experimental setting was applied. Ratio profiles comprising single hybridizations were combined in an error-weighted fashion to create ratio experiments. A two-fold change expression cut off for ratio experiments was applied together with anti-correlation of ratio profiles rendering the microarray analysis set highly significant (P-value > 0.01), robust and reproducible.

ORGANISM(S): Musculus  

SUBMITTER: Manuel Koch  Hans-Joachim Mollenkopf   Thomas F Meyer   Lina Fassi Fehri    

PROVIDER: E-GEOD-18616 | ArrayExpress | 2014-05-01

SECONDARY ACCESSION(S): GSE18616PRJNA121447

REPOSITORIES: GEO, ArrayExpress

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Publications


Amongst the most severe clinical outcomes of life-long infections with Helicobacter pylori is the development of peptic ulcers and gastric adenocarcinoma--diseases often associated with an increase of regulatory T cells. Understanding H. pylori-driven regulation of T cells is therefore of crucial clinical importance. Several studies have defined mammalian microRNAs as key regulators of the immune system and of carcinogenic processes. Hence, we aimed here to identify H. pylori-regulated miRNAs, m  ...[more]

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