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.

Science 27 April 2007:
Vol. 316. no. 5824, pp. 604 - 608
DOI: 10.1126/science.1141229
Prev | Table of Contents | Next

Reports

Regulation of the Germinal Center Response by MicroRNA-155

To-Ha Thai,1 Dinis Pedro Calado,1 Stefano Casola,2 K. Mark Ansel,1 Changchun Xiao,1 Yingzi Xue,3 Andrew Murphy,3 David Frendewey,3 David Valenzuela,3 Jeffery L. Kutok,4 Marc Schmidt-Supprian,1 Nikolaus Rajewsky,5 George Yancopoulos,3 Anjana Rao,1 Klaus Rajewsky1*

MicroRNAs are small RNA species involved in biological control at multiple levels. Using genetic deletion and transgenic approaches, we show that the evolutionarily conserved microRNA-155 (miR-155) has an important role in the mammalian immune system, specifically in regulating T helper cell differentiation and the germinal center reaction to produce an optimal T cell–dependent antibody response. miR-155 exerts this control, at least in part, by regulating cytokine production. These results also suggest that individual microRNAs can exert critical control over mammalian differentiation processes in vivo.

1 CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA.
2 IFOM–The FIRC Institute for Molecular Oncology, Milano, Via Adamello 16 Milan 20139, Italy.
3 Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA.
4 Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
5 Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, D-13125 Berlin, Germany.

* To whom correspondence should be addressed. E-mail: rajewsky{at}cbr.med.harvard.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Annotating non-coding transcription using functional genomics strategies.
A. R. R. Forrest, R. F. Abdelhamid, and P. Carninci (2009)
Brief Funct Genomic Proteomic 8, 437-443
   Abstract »    Full Text »    PDF »
miRNA deregulation by epigenetic silencing disrupts suppression of the oncogene PLAG1 in chronic lymphocytic leukemia.
C. P. Pallasch, M. Patz, Y. J. Park, S. Hagist, D. Eggle, R. Claus, S. Debey-Pascher, A. Schulz, L. P. Frenzel, J. Claasen, et al. (2009)
Blood 114, 3255-3264
   Abstract »    Full Text »    PDF »
MicroRNA dynamics in the stages of tumorigenesis correlate with hallmark capabilities of cancer.
P. Olson, J. Lu, H. Zhang, A. Shai, M. G. Chun, Y. Wang, S. K. Libutti, E. K. Nakakura, T. R. Golub, and D. Hanahan (2009)
Genes & Dev. 23, 2152-2165
   Abstract »    Full Text »    PDF »
miR-147, a microRNA that is induced upon Toll-like receptor stimulation, regulates murine macrophage inflammatory responses.
G. Liu, A. Friggeri, Y. Yang, Y.-J. Park, Y. Tsuruta, and E. Abraham (2009)
PNAS 106, 15819-15824
   Abstract »    Full Text »    PDF »
Loss of Cardiac microRNA-Mediated Regulation Leads to Dilated Cardiomyopathy and Heart Failure.
P. K. Rao, Y. Toyama, H. R. Chiang, S. Gupta, M. Bauer, R. Medvid, F. Reinhardt, R. Liao, M. Krieger, R. Jaenisch, et al. (2009)
Circ. Res. 105, 585-594
   Abstract »    Full Text »    PDF »
Silencing of microRNA-155 in mice during acute inflammatory response leads to derepression of c/ebp Beta and down-regulation of G-CSF.
J. Worm, J. Stenvang, A. Petri, K. S. Frederiksen, S. Obad, J. Elmen, M. Hedtjarn, E. M. Straarup, J. B. Hansen, and S. Kauppinen (2009)
Nucleic Acids Res. 37, 5784-5792
   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 »
Coordinate Regulation of FOXO1 by miR-27a, miR-96, and miR-182 in Breast Cancer Cells.
I. K. Guttilla and B. A. White (2009)
J. Biol. Chem. 284, 23204-23216
   Abstract »    Full Text »    PDF »
Src homology 2 domain-containing inositol-5-phosphatase and CCAAT enhancer-binding protein {beta} are targeted by miR-155 in B cells of E{micro}-MiR-155 transgenic mice.
S. Costinean, S. K. Sandhu, I. M. Pedersen, E. Tili, R. Trotta, D. Perrotti, D. Ciarlariello, P. Neviani, J. Harb, L. R. Kauffman, et al. (2009)
Blood 114, 1374-1382
   Abstract »    Full Text »    PDF »
microRNA 184 regulates expression of NFAT1 in umbilical cord blood CD4+ T cells.
R. P. Weitzel, M. L. Lesniewski, P. Haviernik, S. Kadereit, P. Leahy, N. J. Greco, and M. J. Laughlin (2009)
Blood 113, 6648-6657
   Abstract »    Full Text »    PDF »
MicroRNA-155 Modulates the Pathogen Binding Ability of Dendritic Cells (DCs) by Down-regulation of DC-specific Intercellular Adhesion Molecule-3 Grabbing Non-integrin (DC-SIGN).
R. T. Martinez-Nunez, F. Louafi, P. S. Friedmann, and T. Sanchez-Elsner (2009)
J. Biol. Chem. 284, 16334-16342
   Abstract »    Full Text »    PDF »
Inositol phosphatase SHIP1 is a primary target of miR-155.
R. M. O'Connell, A. A. Chaudhuri, D. S. Rao, and D. Baltimore (2009)
PNAS 106, 7113-7118
   Abstract »    Full Text »    PDF »
MicroRNAs: Regulating a Change of Heart.
K. G. Barringhaus and P. D. Zamore (2009)
Circulation 119, 2217-2224
   Full Text »    PDF »
miR-375 maintains normal pancreatic {alpha}- and {beta}-cell mass.
M. N. Poy, J. Hausser, M. Trajkovski, M. Braun, S. Collins, P. Rorsman, M. Zavolan, and M. Stoffel (2009)
PNAS 106, 5813-5818
   Abstract »    Full Text »    PDF »
Induction and regulatory function of miR-9 in human monocytes and neutrophils exposed to proinflammatory signals.
F. Bazzoni, M. Rossato, M. Fabbri, D. Gaudiosi, M. Mirolo, L. Mori, N. Tamassia, A. Mantovani, M. A. Cassatella, and M. Locati (2009)
PNAS 106, 5282-5287
   Abstract »    Full Text »    PDF »
Shhh! Silencing by microRNA-155.
G. Teng and F. N. Papavasiliou (2009)
Phil Trans R Soc B 364, 631-637
   Abstract »    Full Text »    PDF »
Cutting Edge: The Foxp3 Target miR-155 Contributes to the Development of Regulatory T Cells.
S. Kohlhaas, O. A. Garden, C. Scudamore, M. Turner, K. Okkenhaug, and E. Vigorito (2009)
J. Immunol. 182, 2578-2582
   Abstract »    Full Text »    PDF »
MicroRNAs As Novel Regulators of Angiogenesis.
Y. Suarez and W. C. Sessa (2009)
Circ. Res. 104, 442-454
   Abstract »    Full Text »    PDF »
MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells.
M. Ceppi, P. M. Pereira, I. Dunand-Sauthier, E. Barras, W. Reith, M. A. Santos, and P. Pierre (2009)
PNAS 106, 2735-2740
   Abstract »    Full Text »    PDF »
miR-451 regulates zebrafish erythroid maturation in vivo via its target gata2.
L. Pase, J. E. Layton, W. P. Kloosterman, D. Carradice, P. M. Waterhouse, and G. J. Lieschke (2009)
Blood 113, 1794-1804
   Abstract »    Full Text »    PDF »
Coherent but overlapping expression of microRNAs and their targets during vertebrate development.
A. Shkumatava, A. Stark, H. Sive, and D. P. Bartel (2009)
Genes & Dev. 23, 466-481
   Abstract »    Full Text »    PDF »
HIV-associated lymphomas and gamma-herpesviruses.
A. Carbone, E. Cesarman, M. Spina, A. Gloghini, and T. F. Schulz (2009)
Blood 113, 1213-1224
   Abstract »    Full Text »    PDF »
MicroRNA-221-222 Regulate the Cell Cycle in Mast Cells.
R. J. Mayoral, M. E. Pipkin, M. Pachkov, E. van Nimwegen, A. Rao, and S. Monticelli (2009)
J. Immunol. 182, 433-445
   Abstract »    Full Text »    PDF »
Prostaglandin E2 regulates B cell proliferation through a candidate tumor suppressor, Ptger4.
J. Murn, O. Alibert, N. Wu, S. Tendil, and X. Gidrol (2008)
J. Exp. Med. 205, 3091-3103
   Abstract »    Full Text »    PDF »
Sequence Conservation and Differential Expression of Marek's Disease Virus MicroRNAs.
R. Morgan, A. Anderson, E. Bernberg, S. Kamboj, E. Huang, G. Lagasse, G. Isaacs, M. Parcells, B. C. Meyers, P. J. Green, et al. (2008)
J. Virol. 82, 12213-12220
   Abstract »    Full Text »    PDF »
microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart.
N. Liu, S. Bezprozvannaya, A. H. Williams, X. Qi, J. A. Richardson, R. Bassel-Duby, and E. N. Olson (2008)
Genes & Dev. 22, 3242-3254
   Abstract »    Full Text »    PDF »
Adding fuel to fire: microRNAs as a new class of mediators of inflammation.
F J Sheedy and L A J O'Neill (2008)
Ann Rheum Dis 67, iii50-iii55
   Abstract »    Full Text »    PDF »
MicroRNA-155 Is Regulated by the Transforming Growth Factor {beta}/Smad Pathway and Contributes to Epithelial Cell Plasticity by Targeting RhoA.
W. Kong, H. Yang, L. He, J.-j. Zhao, D. Coppola, W. S. Dalton, and J. Q. Cheng (2008)
Mol. Cell. Biol. 28, 6773-6784
   Abstract »    Full Text »    PDF »
Epstein-Barr virus latent membrane protein 1 trans-activates miR-155 transcription through the NF-{kappa}B pathway.
G. Gatto, A. Rossi, D. Rossi, S. Kroening, S. Bonatti, and M. Mallardo (2008)
Nucleic Acids Res. 36, 6608-6619
   Abstract »    Full Text »    PDF »
Epstein-Barr Virus-Induced miR-155 Attenuates NF-{kappa}B Signaling and Stabilizes Latent Virus Persistence.
F. Lu, A. Weidmer, C.-G. Liu, S. Volinia, C. M. Croce, and P. M. Lieberman (2008)
J. Virol. 82, 10436-10443
   Abstract »    Full Text »    PDF »
Podocyte-Selective Deletion of Dicer Induces Proteinuria and Glomerulosclerosis.
S. Shi, L. Yu, C. Chiu, Y. Sun, J. Chen, G. Khitrov, M. Merkenschlager, L. B. Holzman, W. Zhang, P. Mundel, et al. (2008)
J. Am. Soc. Nephrol. 19, 2159-2169
   Abstract »    Full Text »    PDF »
Dicer1 Is Required for Differentiation of the Mouse Male Germline.
D. M. Maatouk, K. L. Loveland, M. T. McManus, K. Moore, and B. D. Harfe (2008)
Biol Reprod 79, 696-703
   Abstract »    Full Text »    PDF »
Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity.
X. Zhou, L. T. Jeker, B. T. Fife, S. Zhu, M. S. Anderson, M. T. McManus, and J. A. Bluestone (2008)
J. Exp. Med. 205, 1983-1991
   Abstract »    Full Text »    PDF »
The DNA/RNA-Binding Protein, Translin, Binds microRNA122a and Increases Its In Vivo Stability.
Z. Yu and N. B. Hecht (2008)
J Androl 29, 572-579
   Abstract »    Full Text »    PDF »
B lymphocytes: how they develop and function.
T. W. LeBien and T. F. Tedder (2008)
Blood 112, 1570-1580
   Abstract »    Full Text »    PDF »
MicroRNA-Mediated Down-Regulation of PRDM1/Blimp-1 in Hodgkin/Reed-Sternberg Cells: A Potential Pathogenetic Lesion in Hodgkin Lymphomas.
K. Nie, M. Gomez, P. Landgraf, J.-F. Garcia, Y. Liu, L. H.C. Tan, A. Chadburn, T. Tuschl, D. M. Knowles, and W. Tam (2008)
Am. J. Pathol. 173, 242-252
   Abstract »    Full Text »    PDF »
MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia.
M. Jongen-Lavrencic, S. M. Sun, M. K. Dijkstra, P. J. M. Valk, and B. Lowenberg (2008)
Blood 111, 5078-5085
   Abstract »    Full Text »    PDF »
Microribonucleic Acid-21 Increases Aldosterone Secretion and Proliferation in H295R Human Adrenocortical Cells.
D. G. Romero, M. W. Plonczynski, C. A. Carvajal, E. P. Gomez-Sanchez, and C. E. Gomez-Sanchez (2008)
Endocrinology 149, 2477-2483
   Abstract »    Full Text »    PDF »
Rapid Changes in MicroRNA-146a Expression Negatively Regulate the IL-1{beta}-Induced Inflammatory Response in Human Lung Alveolar Epithelial Cells.
M. M. Perry, S. A. Moschos, A. E. Williams, N. J. Shepherd, H. M. Larner-Svensson, and M. A. Lindsay (2008)
J. Immunol. 180, 5689-5698
   Abstract »    Full Text »    PDF »
Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder.
R. M. O'Connell, D. S. Rao, A. A. Chaudhuri, M. P. Boldin, K. D. Taganov, J. Nicoll, R. L. Paquette, and D. Baltimore (2008)
J. Exp. Med. 205, 585-594
   Abstract »    Full Text »    PDF »
Dicer-dependent pathways regulate chondrocyte proliferation and differentiation.
T. Kobayashi, J. Lu, B. S. Cobb, S. J. Rodda, A. P. McMahon, E. Schipani, M. Merkenschlager, and H. M. Kronenberg (2008)
PNAS 105, 1949-1954
   Abstract »    Full Text »    PDF »
B-cell Receptor Activation Induces BIC/miR-155 Expression through a Conserved AP-1 Element.
Q. Yin, X. Wang, J. McBride, C. Fewell, and E. Flemington (2008)
J. Biol. Chem. 283, 2654-2662
   Abstract »    Full Text »    PDF »
Kaposi's Sarcoma-Associated Herpesvirus Encodes an Ortholog of miR-155.
R. L. Skalsky, M. A. Samols, K. B. Plaisance, I. W. Boss, A. Riva, M. C. Lopez, H. V. Baker, and R. Renne (2007)
J. Virol. 81, 12836-12845
   Abstract »    Full Text »    PDF »
The Oncogenic microRNA-27a Targets Genes That Regulate Specificity Protein Transcription Factors and the G2-M Checkpoint in MDA-MB-231 Breast Cancer Cells.
S. U. Mertens-Talcott, S. Chintharlapalli, X. Li, and S. Safe (2007)
Cancer Res. 67, 11001-11011
   Abstract »    Full Text »    PDF »
P68 RNA Helicase Unwinds the Human let-7 MicroRNA Precursor Duplex and Is Required for let-7-directed Silencing of Gene Expression.
D. W. Salzman, J. Shubert-Coleman, and H. Furneaux (2007)
J. Biol. Chem. 282, 32773-32779
   Abstract »    Full Text »    PDF »
Modulation of miR-155 and miR-125b Levels following Lipopolysaccharide/TNF-{alpha} Stimulation and Their Possible Roles in Regulating the Response to Endotoxin Shock.
E. Tili, J.-J. Michaille, A. Cimino, S. Costinean, C. D. Dumitru, B. Adair, M. Fabbri, H. Alder, C. G. Liu, G. A. Calin, et al. (2007)
J. Immunol. 179, 5082-5089
   Abstract »    Full Text »    PDF »
MicroRNA regulation of cyclooxygenase-2 during embryo implantation.
A. Chakrabarty, S. Tranguch, T. Daikoku, K. Jensen, H. Furneaux, and S. K. Dey (2007)
PNAS 104, 15144-15149
   Abstract »    Full Text »    PDF »
Life beyond cleavage: the case of Ago2 and hematopoiesis.
J. Martinez and M. Busslinger (2007)
Genes & Dev. 21, 1983-1988
   Full Text »    PDF »
Micromanagement During the Innate Immune Response.
J. E. Dahlberg and E. Lund (2007)
Sci. STKE 2007, pe25
   Abstract »    Full Text »    PDF »
MicroRNAs with macro effects.
A. Katsnelson (2007)
J. Cell Biol. 177, 568
   Full Text »    PDF »
The Biology of the Germinal Center.
Y. Natkunam (2007)
Hematology 2007, 210-215
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)