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.

Subscribe

Logo for

Science 305 (5687): 1150-1153

Copyright © 2004 by the American Association for the Advancement of Science

Requirement of Rac1 and Rac2 Expression by Mature Dendritic Cells for T Cell Priming

Federica Benvenuti,1*{dagger} Stephanie Hugues,1{dagger} Marita Walmsley,2 Sandra Ruf,2 Luc Fetler,3 Michel Popoff,4 Victor L. J. Tybulewicz,2 Sebastian Amigorena1{ddagger}

Abstract: Upon maturation, dendritic cells (DCs) acquire the unique ability to activate naïve T cells. We used time-lapse video microscopy and two-photon imaging of intact lymph nodes to showthat after establishing initial contact between their dendrites and naïve T lymphocytes, mature DCs migrate toward the contacted lymphocytes. Subsequently, the DCs tightly entrap the T cells within a complex net of membrane extensions. The Rho family guanosine triphosphatases Rac1 and Rac2 but not Rho itself control the formation of dendrites in mature DCs, their polarized short-range migration toward T cells, and T cell priming.

1 Unité INSERM 365, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.
2 Division of Immune Cell Biology, National Institute for Medical Research, Mill Hill, London, NW7 1AA, UK.
3 UMR 168 CNRS/Institut Curie, 11 rue Pierre et Marie Curie, 75005 Paris, France.
4 Institut Pasteur, Unité des Toxines Microbiennes, 75015 Paris, France.

Back to Top

* Present address: International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34121 Trieste, Italy.

{dagger} These authors contributed equally to this work.

{ddagger} To whom correspondence should be addressed. E-mail: sebastian.amigorena{at}curie.fr


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Control of Dendritic Cell Migration, T Cell-Dependent Immunity, and Autoimmunity by Protein Tyrosine Phosphatase PTPN12 Expressed in Dendritic Cells.
I. Rhee, M.-C. Zhong, B. Reizis, C. Cheong, and A. Veillette (2014)
Mol. Cell. Biol. 34, 888-899
   Abstract »    Full Text »    PDF »
TLR4 Signaling Shapes B Cell Dynamics via MyD88-Dependent Pathways and Rac GTPases.
L. Barrio, J. Saez de Guinoa, and Y. R. Carrasco (2013)
J. Immunol. 191, 3867-3875
   Abstract »    Full Text »    PDF »
Robust evidence for five new Graves' disease risk loci from a staged genome-wide association analysis.
S.-X. Zhao, L.-Q. Xue, W. Liu, Z.-H. Gu, C.-M. Pan, S.-Y. Yang, M. Zhan, H.-N. Wang, J. Liang, G.-Q. Gao, et al. (2013)
Hum. Mol. Genet. 22, 3347-3362
   Abstract »    Full Text »    PDF »
Differential requirement for ROCK in dendritic cell migration within lymphatic capillaries in steady-state and inflammation.
M. Nitschke, D. Aebischer, M. Abadier, S. Haener, M. Lucic, B. Vigl, H. Luche, H. J. Fehling, O. Biehlmaier, R. Lyck, et al. (2012)
Blood 120, 2249-2258
   Abstract »    Full Text »    PDF »
Substrate Rigidity Regulates Human T Cell Activation and Proliferation.
R. S. O'Connor, X. Hao, K. Shen, K. Bashour, T. Akimova, W. W. Hancock, L. C. Kam, and M. C. Milone (2012)
J. Immunol. 189, 1330-1339
   Abstract »    Full Text »    PDF »
DOCK8 is a Cdc42 activator critical for interstitial dendritic cell migration during immune responses.
Y. Harada, Y. Tanaka, M. Terasawa, M. Pieczyk, K. Habiro, T. Katakai, K. Hanawa-Suetsugu, M. Kukimoto-Niino, T. Nishizaki, M. Shirouzu, et al. (2012)
Blood 119, 4451-4461
   Abstract »    Full Text »    PDF »
R-Ras is required for murine dendritic cell maturation and CD4+ T-cell priming.
G. Singh, D. Hashimoto, X. Yan, J. Helft, P. J.- Y. Park, G. Ma, R. F. Qiao, C. R. Kennedy, S.-H. Chen, M. Merad, et al. (2012)
Blood 119, 1693-1701
   Abstract »    Full Text »    PDF »
An Evolutionary Analysis of RAC2 Identifies Haplotypes Associated with Human Autoimmune Diseases.
M. Sironi, F. R. Guerini, C. Agliardi, M. Biasin, R. Cagliani, M. Fumagalli, D. Caputo, A. Cassinotti, S. Ardizzone, M. Zanzottera, et al. (2011)
Mol. Biol. Evol. 28, 3319-3329
   Abstract »    Full Text »    PDF »
Cytoskeletal remodeling mediated by WASp in dendritic cells is necessary for normal immune synapse formation and T-cell priming.
G. Bouma, A. Mendoza-Naranjo, M. P. Blundell, E. de Falco, K. L. Parsley, S. O. Burns, and A. J. Thrasher (2011)
Blood 118, 2492-2501
   Abstract »    Full Text »    PDF »
Fascin1 Promotes Cell Migration of Mature Dendritic Cells.
Y. Yamakita, F. Matsumura, M. W. Lipscomb, P.-c. Chou, G. Werlen, J. K. Burkhardt, and S. Yamashiro (2011)
J. Immunol. 186, 2850-2859
   Abstract »    Full Text »    PDF »
Store-operated Ca2+ signaling in dendritic cells occurs independently of STIM1.
B. C. Bandyopadhyay, S. C. Pingle, and G. P. Ahern (2011)
J. Leukoc. Biol. 89, 57-62
   Abstract »    Full Text »    PDF »
Plexin-A4-semaphorin 3A signaling is required for Toll-like receptor- and sepsis-induced cytokine storm.
H. Wen, Y. Lei, S.-Y. Eun, and J. P.-Y. Ting (2010)
J. Exp. Med. 207, 2943-2957
   Abstract »    Full Text »    PDF »
Cdc42-mediated MTOC polarization in dendritic cells controls targeted delivery of cytokines at the immune synapse.
J. Pulecio, J. Petrovic, F. Prete, G. Chiaruttini, A.-M. Lennon-Dumenil, C. Desdouets, S. Gasman, O. R. Burrone, and F. Benvenuti (2010)
J. Exp. Med. 207, 2719-2732
   Abstract »    Full Text »    PDF »
Dendritic Cells Continue To Capture and Present Antigens after Maturation In Vivo.
S. B. Drutman and E. S. Trombetta (2010)
J. Immunol. 185, 2140-2146
   Abstract »    Full Text »    PDF »
Bam32/DAPP1 Promotes B Cell Adhesion and Formation of Polarized Conjugates with T Cells.
M. Al-Alwan, S. Hou, T.-t. Zhang, K. Makondo, and A. J. Marshall (2010)
J. Immunol. 184, 6961-6969
   Abstract »    Full Text »    PDF »
Vav1 Regulates the Migration and Adhesion of Dendritic Cells.
D. R. Spurrell, N. A. Luckashenak, D. C. Minney, A. Chaplin, J. M. Penninger, R. S. Liwski, J. L. Clements, and K. A. West (2009)
J. Immunol. 183, 310-318
   Abstract »    Full Text »    PDF »
Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration.
T. Lammermann, J. Renkawitz, X. Wu, K. Hirsch, C. Brakebusch, and M. Sixt (2009)
Blood 113, 5703-5710
   Abstract »    Full Text »    PDF »
SWAP-70 regulates RhoA/RhoB-dependent MHCII surface localization in dendritic cells.
C. Ocana-Morgner, C. Wahren, and R. Jessberger (2009)
Blood 113, 1474-1482
   Abstract »    Full Text »    PDF »
Structure of the F-spondin domain of mindin, an integrin ligand and pattern recognition molecule.
Y. Li, C. Cao, W. Jia, L. Yu, M. Mo, Q. Wang, Y. Huang, J.-M. Lim, M. Ishihara, L. Wells, et al. (2009)
EMBO J. 28, 286-297
   Abstract »    Full Text »    PDF »
A point mutation in the murine Hem1 gene reveals an essential role for Hematopoietic Protein 1 in lymphopoiesis and innate immunity.
H. Park, K. Staehling-Hampton, M. W. Appleby, M. E. Brunkow, T. Habib, Y. Zhang, F. Ramsdell, H. D. Liggitt, B. Freie, M. Tsang, et al. (2008)
J. Exp. Med. 205, 2899-2913
   Abstract »    Full Text »    PDF »
T Cell-Dendritic Cell Immunological Synapses Contain TCR-dependent CD28-CD80 Clusters That Recruit Protein Kinase C{theta}.
S.-Y. Tseng, J. C. Waite, M. Liu, S. Vardhana, and M. L. Dustin (2008)
J. Immunol. 181, 4852-4863
   Abstract »    Full Text »    PDF »
Involvement of LEK1 in Dendritic Cell Regulation of T Cell Immunity against Chlamydia.
Q. He, F. O. Eko, D. Lyn, G. A. Ananaba, C. Bandea, J. Martinez, K. Joseph, K. Kellar, C. M. Black, and J. U. Igietseme (2008)
J. Immunol. 181, 4037-4042
   Abstract »    Full Text »    PDF »
Rac GTPase isoforms Rac1 and Rac2 play a redundant and crucial role in T-cell development.
F. Guo, J. A. Cancelas, D. Hildeman, D. A. Williams, and Y. Zheng (2008)
Blood 112, 1767-1775
   Abstract »    Full Text »    PDF »
Expression of Wiskott-Aldrich Syndrome Protein in Dendritic Cells Regulates Synapse Formation and Activation of Naive CD8+ T Cells.
J. Pulecio, E. Tagliani, A. Scholer, F. Prete, L. Fetler, O. R. Burrone, and F. Benvenuti (2008)
J. Immunol. 181, 1135-1142
   Abstract »    Full Text »    PDF »
Spinophilin participates in information transfer at immunological synapses.
O. Bloom, J. J. Unternaehrer, A. Jiang, J.-S. Shin, L. Delamarre, P. Allen, and I. Mellman (2008)
J. Cell Biol. 181, 203-211
   Abstract »    Full Text »    PDF »
Leptin as an immunological adjuvant: enhanced migratory and CD8+ T cell stimulatory capacity of human dendritic cells exposed to leptin.
B. Mattioli, E. Straface, P. Matarrese, M. G. Quaranta, L. Giordani, W. Malorni, and M. Viora (2008)
FASEB J 22, 2012-2022
   Abstract »    Full Text »    PDF »
Aberrant dendritic cell differentiation initiated by the Mll-Een fusion gene does not require leukemic transformation.
Q. Sun, C. T. Kong, F. P. Huang, and L. C. Chan (2008)
J. Leukoc. Biol. 83, 173-180
   Abstract »    Full Text »    PDF »
An ITAM-signaling pathway controls cross-presentation of particulate but not soluble antigens in dendritic cells.
D. B. Graham, L. M. Stephenson, S. K. Lam, K. Brim, H. M. Lee, J. Bautista, S. Gilfillan, S. Akilesh, K. Fujikawa, and W. Swat (2007)
J. Exp. Med. 204, 2889-2897
   Abstract »    Full Text »    PDF »
Sphingosine-1 Phosphate Signaling Regulates Positioning of Dendritic Cells within the Spleen.
N. Czeloth, A. Schippers, N. Wagner, W. Muller, B. Kuster, G. Bernhardt, and R. Forster (2007)
J. Immunol. 179, 5855-5863
   Abstract »    Full Text »    PDF »
CCR1/CCL5 (RANTES) receptor-ligand interactions modulate allogeneic T-cell responses and graft-versus-host disease following stem-cell transplantation.
S. W. Choi, G. C. Hildebrandt, K. M. Olkiewicz, D. A. Hanauer, M. N. Chaudhary, I. A. Silva, C. E. Rogers, D. T. Deurloo, J. M. Fisher, C. Liu, et al. (2007)
Blood 110, 3447-3455
   Abstract »    Full Text »    PDF »
Rac1 GTPase Regulates Cell Genomic Stability and Senescence.
M. Debidda, D. A. Williams, and Y. Zheng (2006)
J. Biol. Chem. 281, 38519-38528
   Abstract »    Full Text »    PDF »
Defective Chemokine-Directed Lymphocyte Migration and Development in the Absence of Rho Guanosine Diphosphate-Dissociation Inhibitors {alpha} and beta.
H. Ishizaki, A. Togawa, M. Tanaka-Okamoto, K. Hori, M. Nishimura, A. Hamaguchi, T. Imai, Y. Takai, and J. Miyoshi (2006)
J. Immunol. 177, 8512-8521
   Abstract »    Full Text »    PDF »
Rho GTPase CDC42 regulates directionality and random movement via distinct MAPK pathways in neutrophils.
K. Szczur, H. Xu, S. Atkinson, Y. Zheng, and M.-D. Filippi (2006)
Blood 108, 4205-4213
   Abstract »    Full Text »    PDF »
The Src Homology 2 Domain-Containing Leukocyte Protein of 76-kDa Adaptor Links Integrin Ligation with p44/42 MAPK Phosphorylation and Podosome Distribution in Murine Dendritic Cells.
N. A. Luckashenak, R. L. Ryszkiewicz, K. D. Ramsey, and J. L. Clements (2006)
J. Immunol. 177, 5177-5185
   Abstract »    Full Text »    PDF »
Cutting Edge: Rho Activation and Actin Polarization Are Dependent on Plexin-A1 in Dendritic Cells.
S.-Y. Eun, B. P. O'Connor, A. W. Wong, H. W. van Deventer, D. J. Taxman, W. Reed, P. Li, J. S. Blum, K. P. McKinnon, and J. P.-Y. Ting (2006)
J. Immunol. 177, 4271-4275
   Abstract »    Full Text »    PDF »
Human Cytomegalovirus Alters Localization of MHC Class II and Dendrite Morphology in Mature Langerhans Cells.
A. W. Lee, L. Hertel, R. K. Louie, T. Burster, V. Lacaille, A. Pashine, D. A. Abate, E. S. Mocarski, and E. D. Mellins (2006)
J. Immunol. 177, 3960-3971
   Abstract »    Full Text »    PDF »
Efficient dendritic cell priming of T lymphocytes depends on the extracellular matrix protein mindin.
H. Li, T. Oliver, W. Jia, and Y.-W. He (2006)
EMBO J. 25, 4097-4107
   Abstract »    Full Text »    PDF »
TRIF-GEFH1-RhoB pathway is involved in MHCII expression on dendritic cells that is critical for CD4 T-cell activation.
H. Kamon, T. Kawabe, H. Kitamura, J. Lee, D. Kamimura, T. Kaisho, S. Akira, A. Iwamatsu, H. Koga, M. Murakami, et al. (2006)
EMBO J. 25, 4108-4119
   Abstract »    Full Text »    PDF »
Differential regulation of phagosome maturation in macrophages and dendritic cells mediated by Rho GTPases and ezrin-radixin-moesin (ERM) proteins.
L.-P. Erwig, K. A. McPhilips, M. W. Wynes, A. Ivetic, A. J. Ridley, and P. M. Henson (2006)
PNAS 103, 12825-12830
   Abstract »    Full Text »    PDF »
ICSBP/IRF-8 differentially regulates antigen uptake during dendritic-cell development and affects antigen presentation to CD4+ T cells.
F. Mattei, G. Schiavoni, P. Borghi, M. Venditti, I. Canini, P. Sestili, I. Pietraforte, H. C. Morse III, C. Ramoni, F. Belardelli, et al. (2006)
Blood 108, 609-617
   Abstract »    Full Text »    PDF »
A novel form of immune signaling revealed by transmission of the inflammatory mediator serotonin between dendritic cells and T cells.
P. J. O'Connell, X. Wang, M. Leon-Ponte, C. Griffiths, S. C. Pingle, and G. P. Ahern (2006)
Blood 107, 1010-1017
   Abstract »    Full Text »    PDF »
Genetic deletion of Cdc42GAP reveals a role of Cdc42 in erythropoiesis and hematopoietic stem/progenitor cell survival, adhesion, and engraftment.
L. Wang, L. Yang, M.-D. Filippi, D. A. Williams, and Y. Zheng (2006)
Blood 107, 98-105
   Abstract »    Full Text »    PDF »
CD80 Cytoplasmic Domain Controls Localization of CD28, CTLA-4, and Protein Kinase C{theta} in the Immunological Synapse.
S.-Y. Tseng, M. Liu, and M. L. Dustin (2005)
J. Immunol. 175, 7829-7836
   Abstract »    Full Text »    PDF »
Sphingosine-1-Phosphate Mediates Migration of Mature Dendritic Cells.
N. Czeloth, G. Bernhardt, F. Hofmann, H. Genth, and R. Forster (2005)
J. Immunol. 175, 2960-2967
   Abstract »    Full Text »    PDF »
Protein Kinase C {beta}II Plays an Essential Role in Dendritic Cell Differentiation and Autoregulates Its Own Expression.
P. J. Cejas, L. M. Carlson, J. Zhang, S. Padmanabhan, D. Kolonias, I. Lindner, S. Haley, L. H. Boise, and K. P. Lee (2005)
J. Biol. Chem. 280, 28412-28423
   Abstract »    Full Text »    PDF »
Generation and Characterization of Rac3 Knockout Mice.
S. Corbetta, S. Gualdoni, C. Albertinazzi, S. Paris, L. Croci, G. G. Consalez, and I. de Curtis (2005)
Mol. Cell. Biol. 25, 5763-5776
   Abstract »    Full Text »    PDF »
Synaptic Clusters of MHC Class II Molecules Induced on DCs by Adhesion Molecule-mediated Initial T-Cell Scanning.
H. de la Fuente, M. Mittelbrunn, L. Sanchez-Martin, M. Vicente-Manzanares, A. Lamana, R. Pardi, C. Cabanas, and F. Sanchez-Madrid (2005)
Mol. Biol. Cell 16, 3314-3322
   Abstract »    Full Text »    PDF »
Selective Rac1 inhibition in dendritic cells diminishes apoptotic cell uptake and cross-presentation in vivo.
K. M. Kerksiek, F. Niedergang, P. Chavrier, D. H. Busch, and T. Brocker (2005)
Blood 105, 742-749
   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