Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

PNAS 106 (8): 2735-2740

Copyright © 2009 by the National Academy of Sciences.


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

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

© 2009 by The National Academy of Sciences of the USA

MicroRNA-155 Deficiency Results in Decreased Macrophage Inflammation and Attenuated Atherogenesis in Apolipoprotein E-Deficient Mice.
F. Du, F. Yu, Y. Wang, Y. Hui, K. Carnevale, M. Fu, H. Lu, and D. Fan (2014)
Arterioscler Thromb Vasc Biol 34, 759-767
   Abstract »    Full Text »    PDF »
miR-155 Suppresses Bacterial Clearance in Pseudomonas aeruginosa-Induced Keratitis by Targeting Rheb.
K. Yang, M. Wu, M. Li, D. Li, A. Peng, X. Nie, M. Sun, J. Wang, Y. Wu, Q. Deng, et al. (2014)
The Journal of Infectious Disease
   Abstract »    Full Text »    PDF »
The Role of Ets2 Transcription Factor in the Induction of MicroRNA-155 (miR-155) by Lipopolysaccharide and Its Targeting by Interleukin-10.
S. R. Quinn, N. E. Mangan, B. E. Caffrey, M. P. Gantier, B. R. G. Williams, P. J. Hertzog, C. E. McCoy, and L. A. J. O'Neill (2014)
J. Biol. Chem. 289, 4316-4325
   Abstract »    Full Text »    PDF »
Increased Serum MicroRNA-155 Level Associated with Nonresponsiveness to Hepatitis B Vaccine.
Y. Xiong, S. Chen, L. Liu, Y. Zhao, W. Lin, and J. Ni (2013)
Clin. Vaccine Immunol. 20, 1089-1091
   Abstract »    Full Text »    PDF »
miR-155 Regulates Immune Modulatory Properties of Mesenchymal Stem Cells by Targeting TAK1-binding Protein 2.
C. Xu, G. Ren, G. Cao, Q. Chen, P. Shou, C. Zheng, L. Du, X. Han, M. Jiang, Q. Yang, et al. (2013)
J. Biol. Chem. 288, 11074-11079
   Abstract »    Full Text »    PDF »
PU.1-Dependent Transcriptional Regulation of miR-142 Contributes to Its Hematopoietic Cell-Specific Expression and Modulation of IL-6.
Y. Sun, J. Sun, T. Tomomi, E. Nieves, N. Mathewson, H. Tamaki, R. Evers, and P. Reddy (2013)
J. Immunol. 190, 4005-4013
   Abstract »    Full Text »    PDF »
Pathogenic arterial remodeling: the good and bad of microRNAs.
Y. Wei, A. Schober, and C. Weber (2013)
Am J Physiol Heart Circ Physiol 304, H1050-H1059
   Abstract »    Full Text »    PDF »
Recognition of pathogen-associated nucleic acids by endosomal nucleic acid-sensing toll-like receptors.
X. He, H. Jia, Z. Jing, and D. Liu (2013)
Acta Biochim Biophys Sin 45, 241-258
   Abstract »    Full Text »    PDF »
1,25-Dihydroxyvitamin D Promotes Negative Feedback Regulation of TLR Signaling via Targeting MicroRNA-155-SOCS1 in Macrophages.
Y. Chen, W. Liu, T. Sun, Y. Huang, Y. Wang, D. K. Deb, D. Yoon, J. Kong, R. Thadhani, and Y. C. Li (2013)
J. Immunol. 190, 3687-3695
   Abstract »    Full Text »    PDF »
MicroRNA-92a Negatively Regulates Toll-like Receptor (TLR)-triggered Inflammatory Response in Macrophages by Targeting MKK4 Kinase.
L. Lai, Y. Song, Y. Liu, Q. Chen, Q. Han, W. Chen, T. Pan, Y. Zhang, X. Cao, and Q. Wang (2013)
J. Biol. Chem. 288, 7956-7967
   Abstract »    Full Text »    PDF »
The {alpha}7{beta}0 Isoform of the Complement Regulator C4b-Binding Protein Induces a Semimature, Anti-Inflammatory State in Dendritic Cells.
R. Olivar, A. Luque, M. Naranjo-Gomez, J. Quer, P. Garcia de Frutos, F. E. Borras, S. Rodriguez de Cordoba, A. M. Blom, and J. M. Aran (2013)
J. Immunol. 190, 2857-2872
   Abstract »    Full Text »    PDF »
Rat mir-155 generated from the lncRNA Bic is 'hidden' in the alternate genomic assembly and reveals the existence of novel mammalian miRNAs and clusters.
P. Uva, L. Da Sacco, M. Del Corno, A. Baldassarre, P. Sestili, M. Orsini, A. Palma, S. Gessani, and A. Masotti (2013)
RNA 19, 365-379
   Abstract »    Full Text »    PDF »
MicroRNAs in Immune Response and Macrophage Polarization.
G. Liu and E. Abraham (2013)
Arterioscler Thromb Vasc Biol 33, 170-177
   Abstract »    Full Text »    PDF »
Differential activation and functional specialization of miR-146 and miR-155 in innate immune sensing.
L. N. Schulte, A. J. Westermann, and J. Vogel (2013)
Nucleic Acids Res. 41, 542-553
   Abstract »    Full Text »    PDF »
MicroRNA-7-regulated TLR9 signaling-enhanced growth and metastatic potential of human lung cancer cells by altering the phosphoinositide-3-kinase, regulatory subunit 3/Akt pathway.
L. Xu, Z. Wen, Y. Zhou, Z. Liu, Q. Li, G. Fei, J. Luo, and T. Ren (2013)
Mol. Biol. Cell 24, 42-55
   Abstract »    Full Text »    PDF »
miR-451 Regulates Dendritic Cell Cytokine Responses to Influenza Infection.
C. M. Rosenberger, R. L. Podyminogin, G. Navarro, G.-W. Zhao, P. S. Askovich, M. J. Weiss, and A. Aderem (2012)
J. Immunol. 189, 5965-5975
   Abstract »    Full Text »    PDF »
IL-10-induced microRNA-187 negatively regulates TNF-{alpha}, IL-6, and IL-12p40 production in TLR4-stimulated monocytes.
M. Rossato, G. Curtale, N. Tamassia, M. Castellucci, L. Mori, S. Gasperini, B. Mariotti, M. De Luca, M. Mirolo, M. A. Cassatella, et al. (2012)
PNAS 109, E3101-E3110
   Abstract »    Full Text »    PDF »
A miRNA-regulatory network explains how dysregulated miRNAs perturb oncogenic processes across diverse cancers.
C. L. Plaisier, M. Pan, and N. S. Baliga (2012)
Genome Res. 22, 2302-2314
   Abstract »    Full Text »    PDF »
Decreased microRNA-155 Expression in Ocular Behcet's Disease but Not in Vogt Koyanagi Harada Syndrome.
Q. Zhou, X. Xiao, C. Wang, X. Zhang, F. Li, Y. Zhou, A. Kijlstra, and P. Yang (2012)
Invest. Ophthalmol. Vis. Sci. 53, 5665-5674
   Abstract »    Full Text »    PDF »
The Oncogenic Role of miR-155 in Breast Cancer.
S. Mattiske, R. J. Suetani, P. M. Neilsen, and D. F. Callen (2012)
Cancer Epidemiol. Biomarkers Prev. 21, 1236-1243
   Abstract »    Full Text »    PDF »
miR-146a regulates mechanotransduction and pressure-induced inflammation in small airway epithelium.
Y. Huang, M. Crawford, N. Higuita-Castro, P. Nana-Sinkam, and S. N. Ghadiali (2012)
FASEB J 26, 3351-3364
   Abstract »    Full Text »    PDF »
Pulmonary microRNA profiling in a mouse model of ventilator-induced lung injury.
K. Vaporidi, E. Vergadi, E. Kaniaris, M. Hatziapostolou, E. Lagoudaki, D. Georgopoulos, W. M. Zapol, K. D. Bloch, and D. Iliopoulos (2012)
Am J Physiol Lung Cell Mol Physiol 303, L199-L207
   Abstract »    Full Text »    PDF »
Identification of Resting and Type I IFN-Activated Human NK Cell miRNomes Reveals MicroRNA-378 and MicroRNA-30e as Negative Regulators of NK Cell Cytotoxicity.
P. Wang, Y. Gu, Q. Zhang, Y. Han, J. Hou, L. Lin, C. Wu, Y. Bao, X. Su, M. Jiang, et al. (2012)
J. Immunol. 189, 211-221
   Abstract »    Full Text »    PDF »
Induction of microRNA-155 is TLR- and type IV secretion system-dependent in macrophages and inhibits DNA-damage induced apoptosis.
M. Koch, H.-J. Mollenkopf, U. Klemm, and T. F. Meyer (2012)
PNAS 109, E1153-E1162
   Abstract »    Full Text »    PDF »
Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes.
A. Montecalvo, A. T. Larregina, W. J. Shufesky, D. Beer Stolz, M. L. G. Sullivan, J. M. Karlsson, C. J. Baty, G. A. Gibson, G. Erdos, Z. Wang, et al. (2012)
Blood 119, 756-766
   Abstract »    Full Text »    PDF »
MicroRNAs Regulate Dendritic Cell Differentiation and Function.
M. L. Turner, F. M. Schnorfeil, and T. Brocker (2011)
J. Immunol. 187, 3911-3917
   Abstract »    Full Text »    PDF »
MicroRNA-155 Promotes Resolution of Hypoxia-Inducible Factor 1{alpha} Activity during Prolonged Hypoxia.
U. Bruning, L. Cerone, Z. Neufeld, S. F. Fitzpatrick, A. Cheong, C. C. Scholz, D. A. Simpson, M. O. Leonard, M. M. Tambuwala, E. P. Cummins, et al. (2011)
Mol. Cell. Biol. 31, 4087-4096
   Abstract »    Full Text »    PDF »
MicroRNA-155 Is Essential for the T Cell-Mediated Control of Helicobacter pylori Infection and for the Induction of Chronic Gastritis and Colitis.
M. Oertli, D. B. Engler, E. Kohler, M. Koch, T. F. Meyer, and A. Muller (2011)
J. Immunol. 187, 3578-3586
   Abstract »    Full Text »    PDF »
MicroRNA function in myeloid biology.
R. M. O'Connell, J. L. Zhao, and D. S. Rao (2011)
Blood 118, 2960-2969
   Abstract »    Full Text »    PDF »
Inhibition of MicroRNA let-7i Depresses Maturation and Functional State of Dendritic Cells in Response to Lipopolysaccharide Stimulation via Targeting Suppressor of Cytokine Signaling 1.
M. Zhang, F. Liu, H. Jia, Q. Zhang, L. Yin, W. Liu, H. Li, B. Yu, and J. Wu (2011)
J. Immunol. 187, 1674-1683
   Abstract »    Full Text »    PDF »
MicroRNA Expression Profiles of Human Blood Monocyte-derived Dendritic Cells and Macrophages Reveal miR-511 as Putative Positive Regulator of Toll-like Receptor 4.
L. Tserel, T. Runnel, K. Kisand, M. Pihlap, L. Bakhoff, R. Kolde, H. Peterson, J. Vilo, P. Peterson, and A. Rebane (2011)
J. Biol. Chem. 286, 26487-26495
   Abstract »    Full Text »    PDF »
MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis.
M. Kurowska-Stolarska, S. Alivernini, L. E. Ballantine, D. L. Asquith, N. L. Millar, D. S. Gilchrist, J. Reilly, M. Ierna, A. R. Fraser, B. Stolarski, et al. (2011)
PNAS 108, 11193-11198
   Abstract »    Full Text »    PDF »
Analysis of microRNA turnover in mammalian cells following Dicer1 ablation.
M. P. Gantier, C. E. McCoy, I. Rusinova, D. Saulep, D. Wang, D. Xu, A. T. Irving, M. A. Behlke, P. J. Hertzog, F. Mackay, et al. (2011)
Nucleic Acids Res. 39, 5692-5703
   Abstract »    Full Text »    PDF »
A trio of microRNAs that control Toll-like receptor signalling.
S. R. Quinn and L. A. O'Neill (2011)
Int. Immunol. 23, 421-425
   Abstract »    Full Text »    PDF »
MicroRNA-155 is involved in the remodelling of human-trophoblast-derived HTR-8/SVneo cells induced by lipopolysaccharides.
Y. Dai, Z. Diao, H. Sun, R. Li, Z. Qiu, and Y. Hu (2011)
Hum. Reprod. 26, 1882-1891
   Abstract »    Full Text »    PDF »
A mini-review: microRNA in arthritis.
T. Nakasa, Y. Nagata, K. Yamasaki, and M. Ochi (2011)
Physiol Genomics 43, 566-570
   Abstract »    Full Text »    PDF »
Analysis of the host microRNA response to Salmonella uncovers the control of major cytokines by the let-7 family.
L. N. Schulte, A. Eulalio, H.-J. Mollenkopf, R. Reinhardt, and J. Vogel (2011)
EMBO J. 30, 1977-1989
   Abstract »    Full Text »    PDF »
Silencing of c-Fos expression by microRNA-155 is critical for dendritic cell maturation and function.
I. Dunand-Sauthier, M.-L. Santiago-Raber, L. Capponi, C. E. Vejnar, O. Schaad, M. Irla, Q. Seguin-Estevez, P. Descombes, E. M. Zdobnov, H. Acha-Orbea, et al. (2011)
Blood 117, 4490-4500
   Abstract »    Full Text »    PDF »
miR-221 and miR-155 regulate human dendritic cell development, apoptosis, and IL-12 production through targeting of p27kip1, KPC1, and SOCS-1.
C. Lu, X. Huang, X. Zhang, K. Roensch, Q. Cao, K. I. Nakayama, B. R. Blazar, Y. Zeng, and X. Zhou (2011)
Blood 117, 4293-4303
   Abstract »    Full Text »    PDF »
Both miR-17-5p and miR-20a Alleviate Suppressive Potential of Myeloid-Derived Suppressor Cells by Modulating STAT3 Expression.
M. Zhang, Q. Liu, S. Mi, X. Liang, Z. Zhang, X. Su, J. Liu, Y. Chen, M. Wang, Y. Zhang, et al. (2011)
J. Immunol. 186, 4716-4724
   Abstract »    Full Text »    PDF »
The Interleukin 13 (IL-13) Pathway in Human Macrophages Is Modulated by MicroRNA-155 via Direct Targeting of Interleukin 13 Receptor {alpha}1 (IL13R{alpha}1).
R. T. Martinez-Nunez, F. Louafi, and T. Sanchez-Elsner (2011)
J. Biol. Chem. 286, 1786-1794
   Abstract »    Full Text »    PDF »
MicroRNA-155 Targets SMAD2 and Modulates the Response of Macrophages to Transforming Growth Factor-{beta}.
F. Louafi, R. T. Martinez-Nunez, and T. Sanchez-Elsner (2010)
J. Biol. Chem. 285, 41328-41336
   Abstract »    Full Text »    PDF »
miR-155 and its star-form partner miR-155* cooperatively regulate type I interferon production by human plasmacytoid dendritic cells.
H. Zhou, X. Huang, H. Cui, X. Luo, Y. Tang, S. Chen, L. Wu, and N. Shen (2010)
Blood 116, 5885-5894
   Abstract »    Full Text »    PDF »
MicroRNA-148/152 Impair Innate Response and Antigen Presentation of TLR-Triggered Dendritic Cells by Targeting CaMKII{alpha}.
X. Liu, Z. Zhan, L. Xu, F. Ma, D. Li, Z. Guo, N. Li, and X. Cao (2010)
J. Immunol. 185, 7244-7251
   Abstract »    Full Text »    PDF »
Inducible microRNA-155 Feedback Promotes Type I IFN Signaling in Antiviral Innate Immunity by Targeting Suppressor of Cytokine Signaling 1.
P. Wang, J. Hou, L. Lin, C. Wang, X. Liu, D. Li, F. Ma, Z. Wang, and X. Cao (2010)
J. Immunol. 185, 6226-6233
   Abstract »    Full Text »    PDF »
Estrogen Induces Distinct Patterns of MicroRNA Expression Within the Mouse Uterus.
W. B. Nothnick and C. Healy (2010)
Reproductive Sciences 17, 987-994
   Abstract »    PDF »
Dicer-Dependent MicroRNAs Control Maturation, Function, and Maintenance of Langerhans Cells In Vivo.
H. Kuipers, F. M. Schnorfeil, H.-J. Fehling, H. Bartels, and T. Brocker (2010)
J. Immunol. 185, 400-409
   Abstract »    Full Text »    PDF »
MicroRNA-155 Regulates Cell Survival, Growth, and Chemosensitivity by Targeting FOXO3a in Breast Cancer.
W. Kong, L. He, M. Coppola, J. Guo, N. N. Esposito, D. Coppola, and J. Q. Cheng (2010)
J. Biol. Chem. 285, 17869-17879
   Abstract »    Full Text »    PDF »
Small RNAs Guide Hematopoietic Cell Differentiation and Function.
F. Navarro and J. Lieberman (2010)
J. Immunol. 184, 5939-5947
   Abstract »    Full Text »    PDF »
Estradiol Suppresses NF-{kappa}B Activation through Coordinated Regulation of let-7a and miR-125b in Primary Human Macrophages.
A. J. Murphy, P. M. Guyre, and P. A. Pioli (2010)
J. Immunol. 184, 5029-5037
   Abstract »    Full Text »    PDF »
MicroRNA-155 Functions as an OncomiR in Breast Cancer by Targeting the Suppressor of Cytokine Signaling 1 Gene.
S. Jiang, H. W. Zhang, M. H. Lu, X. H. He, Y. Li, H. Gu, M. F. Liu, and E. D. Wang (2010)
Cancer Res. 70, 3119-3127
   Abstract »    Full Text »    PDF »
MicroRNA-21 is upregulated during the proliferative phase of liver regeneration, targets Pellino-1, and inhibits NF-{kappa}B signaling.
R. T. Marquez, E. Wendlandt, C. S. Galle, K. Keck, and A. P. McCaffrey (2010)
Am J Physiol Gastrointest Liver Physiol 298, G535-G541
   Abstract »    Full Text »    PDF »
MicroRNA Regulation of IFN-{beta} Protein Expression: Rapid and Sensitive Modulation of the Innate Immune Response.
K. W. Witwer, J. M. Sisk, L. Gama, and J. E. Clements (2010)
J. Immunol. 184, 2369-2376
   Abstract »    Full Text »    PDF »
Reticuloendotheliosis Virus Strain T Induces miR-155, Which Targets JARID2 and Promotes Cell Survival.
M. T. Bolisetty, G. Dy, W. Tam, and K. L. Beemon (2009)
J. Virol. 83, 12009-12017
   Abstract »    Full Text »    PDF »
Antagonism of microRNA-126 suppresses the effector function of TH2 cells and the development of allergic airways disease.
J. Mattes, A. Collison, M. Plank, S. Phipps, and P. S. Foster (2009)
PNAS 106, 18704-18709
   Abstract »    Full Text »    PDF »
Plerixafor (AMD3100) and granulocyte colony-stimulating factor (G-CSF) mobilize different CD34+ cell populations based on global gene and microRNA expression signatures.
R. E. Donahue, P. Jin, A. C. Bonifacino, M. E. Metzger, J. Ren, E. Wang, and D. F. Stroncek (2009)
Blood 114, 2530-2541
   Abstract »    Full Text »    PDF »
LPS induces KH-type splicing regulatory protein-dependent processing of microRNA-155 precursors in macrophages.
T. Ruggiero, M. Trabucchi, F. De Santa, S. Zupo, B. D. Harfe, M. T. McManus, M. G. Rosenfeld, P. Briata, and R. Gherzi (2009)
FASEB J 23, 2898-2908
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882