SEARCH:   Advanced

Blood, 1 August 2004, Vol. 104, No. 3, pp. 619-625. Prepublished online as a Blood First Edition Paper on April 1, 2004; DOI 10.1182/blood-2003-11-3943. This Article Full Text (PDF) All Versions of this Article: 2003-11-3943v1 104/3/619    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sanchez-Sanchez, N. Articles by Rodriguez-Fernandez, J. L. Search for Related Content PubMed PubMed Citation Articles by Sanchez-Sanchez, N. Articles by Rodriguez-Fernandez, J. L. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 18, 2003 Accepted March 24, 2004 Chemokine Receptor CCR7 Induces Intracellular signaling that Inhibits Apoptosis of Mature Dendritic Cells Noelia Sanchez-Sanchez, Lorena Riol-Blanco, Gonzalo de la Rosa, Amaya Puig-Kroger, Julio Garcia-Bordas, Daniel Martin, Natividad Longo, Antonio Cuadrado, Carlos Cabanas, Angel L. Corbi, Paloma Sanchez-Mateos, and Jose Luis Rodriguez-Fernandez* Departamento de Inmunologia, Centro de Investigaciones Biologicas. Consejo Superior de Investigaciones Cientificas, Madrid, Spain Laboratorio de Inmunologia., Hospital General Universitario Gregorio Maranon, Madrid, Spain Instituto de Investigaciones Biomedicas Alberto Sols., Facultad de Medicina. Universidad Autonoma., Madrid, Spain Instituto de Farmacologia y Toxicologia CSIC-UCM, Facultad de Medicina, Universidad Complutense., Madrid, Spain * Corresponding author; email: rodrifer{at}cib.csic.es. Acquisition of CCR7 expression is an important phenotype change during dendritic cell (DC) maturation that endows these cells with the capability to migrate to lymph nodes. We have analyzed the possible role of CCR7 on the regulation of the survival of DCs. Stimulation with CCR7 ligands CCL19 and CCL21 inhibits apoptotic hallmarks of serum deprived DCs, including membrane phosphatidyl-serine exposure, loss of mitochondria membrane potential, increased membrane blebs and nuclear changes. Both chemokines induced a rapid activation of PI3K/Akt1, with a prolonged and persistent activation of Akt1. Interference with PI3K, Gi or G-protein subunits abrogated the effects of the chemokines on Akt1 activation and on survival. In contrast, inhibition of Erk1/2, p38 or JNK was ineffective. NFB was involved in the anti-apoptotic effects of chemokines because inhibition of NFB blunted the effects of CCL19 and CCL21 on survival. Furthermore, chemokines induced down-regulation of the NFB inhibitor IB, increase of NFB binding DNA capability and translocation of the NFB subunit p65 to the nucleus. In summary, in addition to its well-established role in chemotaxis, we show that CCR7 also induces anti-apoptotic signaling in mature DCs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Escribano, C. Delgado-Martin, and J. L. Rodriguez-Fernandez CCR7-Dependent Stimulation of Survival in Dendritic Cells Involves Inhibition of GSK3{beta} J. Immunol., November 15, 2009; 183(10): 6282 - 6295. [Abstract] [Full Text] [PDF] A. J. Hartigan, J. Westwick, G. Jarai, and C. M. Hogaboam CCR7 Deficiency on Dendritic Cells Enhances Fungal Clearance in a Murine Model of Pulmonary Invasive Aspergillosis J. Immunol., October 15, 2009; 183(8): 5171 - 5179. [Abstract] [Full Text] [PDF] S. Alzabin, N. Bhardwaj, F. Kiefer, S. Sawasdikosol, and S. Burakoff Hematopoietic Progenitor Kinase 1 Is a Negative Regulator of Dendritic Cell Activation J. Immunol., May 15, 2009; 182(10): 6187 - 6194. [Abstract] [Full Text] [PDF] B. M. Janelsins, A. R. Mathers, O. A. Tkacheva, G. Erdos, W. J. Shufesky, A. E. Morelli, and A. T. Larregina Proinflammatory tachykinins that signal through the neurokinin 1 receptor promote survival of dendritic cells and potent cellular immunity Blood, March 26, 2009; 113(13): 3017 - 3026. [Abstract] [Full Text] [PDF] C. Otero, P. S. Eisele, K. Schaeuble, M. Groettrup, and D. F. Legler Distinct motifs in the chemokine receptor CCR7 regulate signal transduction, receptor trafficking and chemotaxis J. Cell Sci., August 15, 2008; 121(16): 2759 - 2767. [Abstract] [Full Text] [PDF] J. Wang, R. R. Seethala, Q. Zhang, W. Gooding, C. van Waes, H. Hasegawa, and R. L. Ferris Autocrine and Paracrine Chemokine Receptor 7 Activation in Head and Neck Cancer: Implications for Therapy J Natl Cancer Inst, April 2, 2008; 100(7): 502 - 512. [Abstract] [Full Text] [PDF] C. Rival, V. A. Guazzone, W. von Wulffen, H. Hackstein, E. Schneider, L. Lustig, A. Meinhardt, and M. Fijak Expression of co-stimulatory molecules, chemokine receptors and proinflammatory cytokines in dendritic cells from normal and chronically inflamed rat testis Mol. Hum. Reprod., December 1, 2007; 13(12): 853 - 861. [Abstract] [Full Text] [PDF] E. Ziegler, M. Oberbarnscheidt, S. Bulfone-Paus, R. Forster, U. Kunzendorf, and S. Krautwald CCR7 Signaling Inhibits T Cell Proliferation J. Immunol., November 15, 2007; 179(10): 6485 - 6493. [Abstract] [Full Text] [PDF] H. Unsoeld, K. Mueller, U. Schleicher, C. Bogdan, J. Zwirner, D. Voehringer, and H. Pircher Abrogation of CCL21 chemokine function by transgenic over-expression impairs T cell immunity to local infections Int. Immunol., November 1, 2007; 19(11): 1281 - 1289. [Abstract] [Full Text] [PDF] E. M. Pierce, K. Carpenter, C. Jakubzick, S. L. Kunkel, H. Evanoff, K. R. Flaherty, F. J. Martinez, G. B. Toews, and C. M. Hogaboam Idiopathic pulmonary fibrosis fibroblasts migrate and proliferate to CC chemokine ligand 21 Eur. Respir. J., June 1, 2007; 29(6): 1082 - 1093. [Abstract] [Full Text] [PDF] T. Yasuda, T. Kuwabara, H. Nakano, K. Aritomi, T. Onodera, M. Lipp, Y. Takahama, and T. Kakiuchi Chemokines CCL19 and CCL21 promote activation-induced cell death of antigen-responding T cells Blood, January 15, 2007; 109(2): 449 - 456. [Abstract] [Full Text] [PDF] U. Thanarajasingam, L. Sanz, R. Diaz, J. Qiao, L. Sanchez-Perez, T. Kottke, J. Thompson, J. Chester, and R. G. Vile Delivery of CCL21 to Metastatic Disease Improves the Efficacy of Adoptive T-Cell Therapy Cancer Res., January 1, 2007; 67(1): 300 - 308. [Abstract] [Full Text] [PDF] C. Otero, M. Groettrup, and D. F. Legler Opposite Fate of Endocytosed CCR7 and Its Ligands: Recycling versus Degradation J. Immunol., August 15, 2006; 177(4): 2314 - 2323. [Abstract] [Full Text] [PDF] N. Sanchez-Sanchez, L. Riol-Blanco, and J. L. Rodriguez-Fernandez The Multiple Personalities of the Chemokine Receptor CCR7 in Dendritic Cells J. Immunol., May 1, 2006; 176(9): 5153 - 5159. [Abstract] [Full Text] [PDF] H. Miyazaki, V. Patel, H. Wang, R. K. Edmunds, J. S. Gutkind, and W. A. Yeudall Down-regulation of CXCL5 Inhibits Squamous Carcinogenesis. Cancer Res., April 15, 2006; 66(8): 4279 - 4284. [Abstract] [Full Text] [PDF] L. Frasca, G. Fedele, S. Deaglio, C. Capuano, R. Palazzo, T. Vaisitti, F. Malavasi, and C. M. Ausiello CD38 orchestrates migration, survival, and Th1 immune response of human mature dendritic cells Blood, March 15, 2006; 107(6): 2392 - 2399. [Abstract] [Full Text] [PDF] M. H. Jang, N. Sougawa, T. Tanaka, T. Hirata, T. Hiroi, K. Tohya, Z. Guo, E. Umemoto, Y. Ebisuno, B.-G. Yang, et al. CCR7 Is Critically Important for Migration of Dendritic Cells in Intestinal Lamina Propria to Mesenteric Lymph Nodes J. Immunol., January 15, 2006; 176(2): 803 - 810. [Abstract] [Full Text] [PDF] G. Parmiani, C. Castelli, and L. Rivoltini Chemokine Receptor 7, A New Player in Regulating Apoptosis of CD8+ T Cells in Cancer Patients Clin. Cancer Res., November 1, 2005; 11(21): 7587 - 7588. [Full Text] [PDF] J.-W. Kim, R. L. Ferris, and T. L. Whiteside Chemokine C Receptor 7 Expression and Protection of Circulating CD8+ T Lymphocytes from Apoptosis Clin. Cancer Res., November 1, 2005; 11(21): 7901 - 7910. [Abstract] [Full Text] [PDF] A. Kaiser, E. Donnadieu, J.-P. Abastado, A. Trautmann, and A. Nardin CC Chemokine Ligand 19 Secreted by Mature Dendritic Cells Increases Naive T Cell Scanning Behavior and Their Response to Rare Cognate Antigen J. Immunol., August 15, 2005; 175(4): 2349 - 2356. [Abstract] [Full Text] [PDF] L. Riol-Blanco, N. Sanchez-Sanchez, A. Torres, A. Tejedor, S. Narumiya, A. L. Corbi, P. Sanchez-Mateos, and J. L. Rodriguez-Fernandez The Chemokine Receptor CCR7 Activates in Dendritic Cells Two Signaling Modules That Independently Regulate Chemotaxis and Migratory Speed J. Immunol., April 1, 2005; 174(7): 4070 - 4080. [Abstract] [Full Text] [PDF] K. McKenna, A.-S. Beignon, and N. Bhardwaj Plasmacytoid Dendritic Cells: Linking Innate and Adaptive Immunity J. Virol., January 1, 2005; 79(1): 17 - 27. [Full Text] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020