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PNAS 106 (8): 2735-2740

Copyright © 2009 by the National Academy of Sciences.


BIOLOGICAL SCIENCES / IMMUNOLOGY

MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells

Maurizio Ceppia,b,c,1, Patricia M. Pereirad,e, Isabelle Dunand-Sauthierf, Emmanuèle Barrasf, Walter Reithf, Manuel A. Santosd, and Philippe Pierrea,b,c,2

aCentre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Case 906, 13288 Marseille cedex 9, France; bInstitut National de la Santé et de la Recherche Médicale, U631, 13288 Marseille, France; cCentre National de la Recherche Scientifique, Unité Mixte de Recherche 6102, 13288 Marseille, France; dDepartment of Biology and Centre for Environmental and Marine Studies, University of Aveiro, Aveiro, Portugal; eCentro de Investigação em Meio Ambiente, Genética e Oncobiologia, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; and fDepartment of Pathology and Immunology, University of Geneva Medical School, CH-1211 Geneva, Switzerland

Edited by Ralph M. Steinman, The Rockefeller University, New York, NY, and approved December 24, 2008

Received for publication November 4, 2008.

Abstract: In response to inflammatory stimulation, dendritic cells (DCs) have a remarkable pattern of differentiation (maturation) that exhibits specific mechanisms to control immunity. Here, we show that in response to Lipopolysaccharides (LPS), several microRNAs (miRNAs) are regulated in human monocyte-derived dendritic cells. Among these miRNAs, miR-155 is highly up-regulated during maturation. Using LNA silencing combined to microarray technology, we have identified the Toll-like receptor/interleukin-1 (TLR/IL-1) inflammatory pathway as a general target of miR-155. We further demonstrate that miR-155 directly controls the level of TAB2, an important signal transduction molecule. Our observations suggest, therefore, that in mature human DCs, miR-155 is part of a negative feedback loop, which down-modulates inflammatory cytokine production in response to microbial stimuli.

Key Words: bic/miR-155 • LPS • TAB2 • TLR/IL-1 pathway


Author contributions: M.C., P.M.P., I.D.-S., and P.P. designed research; M.C., P.M.P., I.D.-S., and E.B. performed research; W.R. and M.A.S. contributed new reagents/analytic tools; M.C., P.M.P., I.D.-S., W.R., M.A.S., and P.P. analyzed data; and M.C. and P.M.P. wrote the paper.

1Present address: Genomic Vision, Paris Santé, Cochin, 75014 Paris, France.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. GSE13296).

This article contains supporting information online at www.pnas.org/cgi/content/full/0811073106/DCSupplemental.

2To whom correspondence should be addressed. E-mail: pierre{at}ciml.univ-mrs.fr

© 2009 by The National Academy of Sciences of the USA


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