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 317 (5838): 670-674

Copyright © 2007 by the American Association for the Advancement of Science

Regulation of Homeostatic Chemokine Expression and Cell Trafficking During Immune Responses

Scott N. Mueller,1* Karoline A. Hosiawa-Meagher,2 Bogumila T. Konieczny,1 Brandon M. Sullivan,3 Martin F. Bachmann,4 Richard M. Locksley,3 Rafi Ahmed,1 Mehrdad Matloubian2

Abstract: The chemokines CCL21 and CXCL13 are immune factors that dictate homing and motility of lymphocytes and dendritic cells in lymphoid tissues. However, the means by which these chemokines are regulated and how they influence cell trafficking during immune responses remain unclear. We show that CCL21 and CXCL13 are transiently down-regulated within lymphoid tissues during immune responses by a mechanism controlled by the cytokine interferon-{gamma}. This modulation was found to alter the localization of lymphocytes and dendritic cells within responding lymphoid tissues. As a consequence, priming of T cell responses to a second distinct pathogen after chemokine modulation became impaired. We propose that this transient chemokine modulation may help orchestrate local cellularity, thus minimizing competition for space and resources in activated lymphoid tissues.

1 Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
2 Department of Medicine, Division of Rheumatology, University of California, San Francisco, CA 94143, USA.
3 Howard Hughes Medical Institute and Department of Medicine and Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA.
4 Cytos Biotechnology AG, Wagisstrasse 25, 8952 Schlieren, Switzerland.

* To whom correspondence should be addressed. E-mail: mueller{at}microbio.emory.edu


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Trapping of naive lymphocytes triggers rapid growth and remodeling of the fibroblast network in reactive murine lymph nodes.
C.-Y. Yang, T. K. Vogt, S. Favre, L. Scarpellino, H.-Y. Huang, F. Tacchini-Cottier, and S. A. Luther (2014)
PNAS 111, E109-E118
   Abstract »    Full Text »    PDF »
Regulatory T Cells Suppress the Late Phase of the Immune Response in Lymph Nodes through P-Selectin Glycoprotein Ligand-1.
S. Angiari, B. Rossi, L. Piccio, B. H. Zinselmeyer, S. Budui, E. Zenaro, V. Della Bianca, S. D. Bach, E. Scarpini, M. Bolomini-Vittori, et al. (2013)
J. Immunol. 191, 5489-5500
   Abstract »    Full Text »    PDF »
The role of dendritic cells in driving genital tract inflammation and HIV transmission risk: Are there opportunities to intervene?.
M. S. Shey, N. J. Garrett, L. R. McKinnon, and J.-A. S. Passmore (2013)
Innate Immunity
   Abstract »    Full Text »    PDF »
Virus-associated activation of innate immunity induces rapid disruption of Peyer's patches in mice.
S. Heidegger, D. Anz, N. Stephan, B. Bohn, T. Herbst, W. P. Fendler, N. Suhartha, N. Sandholzer, S. Kobold, C. Hotz, et al. (2013)
Blood 122, 2591-2599
   Abstract »    Full Text »    PDF »
A Chemokine-Like Viral Protein Enhances Alpha Interferon Production by Plasmacytoid Dendritic Cells but Delays CD8+ T Cell Activation and Impairs Viral Clearance.
M. E. Wikstrom, P. Fleming, I. Comerford, S. R. McColl, C. E. Andoniou, and M. A. Degli-Esposti (2013)
J. Virol. 87, 7911-7920
   Abstract »    Full Text »    PDF »
Naive B-cell trafficking is shaped by local chemokine availability and LFA-1-independent stromal interactions.
F. M. Coelho, D. Natale, S. F. Soriano, M. Hons, J. Swoger, J. Mayer, R. Danuser, E. Scandella, M. Pieczyk, H.-G. Zerwes, et al. (2013)
Blood 121, 4101-4109
   Abstract »    Full Text »    PDF »
IL-7-producing stromal cells are critical for lymph node remodeling.
L. Onder, P. Narang, E. Scandella, Q. Chai, M. Iolyeva, K. Hoorweg, C. Halin, E. Richie, P. Kaye, J. Westermann, et al. (2012)
Blood 120, 4675-4683
   Abstract »    Full Text »    PDF »
Retention of Anergy and Inhibition of Antibody Responses during Acute Gammaherpesvirus 68 Infection.
A. Getahun, M. J. Smith, I. Kogut, L. F. van Dyk, and J. C. Cambier (2012)
J. Immunol. 189, 2965-2974
   Abstract »    Full Text »    PDF »
Immortalized clones of fibroblastic reticular cells activate virus-specific T cells during virus infection.
C. T. Ng, B. P. Nayak, C. Schmedt, and M. B. A. Oldstone (2012)
PNAS 109, 7823-7828
   Abstract »    Full Text »    PDF »
Bcl6 and Maf Cooperate To Instruct Human Follicular Helper CD4 T Cell Differentiation.
M. A. Kroenke, D. Eto, M. Locci, M. Cho, T. Davidson, E. K. Haddad, and S. Crotty (2012)
J. Immunol. 188, 3734-3744
   Abstract »    Full Text »    PDF »
Expansion of Cortical and Medullary Sinuses Restrains Lymph Node Hypertrophy during Prolonged Inflammation.
K. W. Tan, K. P. Yeo, F. H. S. Wong, H. Y. Lim, K. L. Khoo, J.-P. Abastado, and V. Angeli (2012)
J. Immunol. 188, 4065-4080
   Abstract »    Full Text »    PDF »
Lymph Node Hypertrophy following Leishmania major Infection Is Dependent on TLR9.
L. P. Carvalho, P. M. Petritus, A. L. Trochtenberg, C. Zaph, D. A. Hill, D. Artis, and P. Scott (2012)
J. Immunol. 188, 1394-1401
   Abstract »    Full Text »    PDF »
Impaired lymphatic contraction associated with immunosuppression.
S. Liao, G. Cheng, D. A. Conner, Y. Huang, R. S. Kucherlapati, L. L. Munn, N. H. Ruddle, R. K. Jain, D. Fukumura, and T. P. Padera (2011)
PNAS 108, 18784-18789
   Abstract »    Full Text »    PDF »
Chemokine receptor CXCR3 facilitates CD8+ T cell differentiation into short-lived effector cells leading to memory degeneration.
M. Kurachi, J. Kurachi, F. Suenaga, T. Tsukui, J. Abe, S. Ueha, M. Tomura, K. Sugihara, S. Takamura, K. Kakimi, et al. (2011)
J. Exp. Med. 208, 1605-1620
   Abstract »    Full Text »    PDF »
Virus-Induced Transient Immune Suppression and the Inhibition of T Cell Proliferation by Type I Interferon.
H. D. Marshall, S. L. Urban, and R. M. Welsh (2011)
J. Virol. 85, 5929-5939
   Abstract »    Full Text »    PDF »
Factors Supporting Intrathecal Humoral Responses following Viral Encephalomyelitis.
T. W. Phares, C. P. Marques, S. A. Stohlman, D. R. Hinton, and C. C. Bergmann (2011)
J. Virol. 85, 2589-2598
   Abstract »    Full Text »    PDF »
CXCR7 influences leukocyte entry into the CNS parenchyma by controlling abluminal CXCL12 abundance during autoimmunity.
L. Cruz-Orengo, D. W. Holman, D. Dorsey, L. Zhou, P. Zhang, M. Wright, E. E. McCandless, J. R. Patel, G. D. Luker, D. R. Littman, et al. (2011)
J. Exp. Med. 208, 327-339
   Abstract »    Full Text »    PDF »
Antibody to Receptor Activator of NF-{kappa}B Ligand Ameliorates T Cell-Mediated Periodontal Bone Resorption.
X. Lin, X. Han, T. Kawai, and M. A. Taubman (2011)
Infect. Immun. 79, 911-917
   Abstract »    Full Text »    PDF »
Global lymphoid tissue remodeling during a viral infection is orchestrated by a B cell-lymphotoxin-dependent pathway.
V. Kumar, E. Scandella, R. Danuser, L. Onder, M. Nitschke, Y. Fukui, C. Halin, B. Ludewig, and J. V. Stein (2010)
Blood 115, 4725-4733
   Abstract »    Full Text »    PDF »
Transmural Flow Modulates Cell and Fluid Transport Functions of Lymphatic Endothelium.
D. O. Miteva, J. M. Rutkowski, J. B. Dixon, W. Kilarski, J. D. Shields, and M. A. Swartz (2010)
Circ. Res. 106, 920-931
   Abstract »    Full Text »    PDF »
Expression of Podoplanin and Other Lymphatic Markers in the Human Anterior Eye Segment.
K. Birke, E. Lutjen-Drecoll, D. Kerjaschki, and M. T. Birke (2010)
Invest. Ophthalmol. Vis. Sci. 51, 344-354
   Abstract »    Full Text »    PDF »
Fluid Flow Regulates Stromal Cell Organization and CCL21 Expression in a Tissue-Engineered Lymph Node Microenvironment.
A. A. Tomei, S. Siegert, M. R. Britschgi, S. A. Luther, and M. A. Swartz (2009)
J. Immunol. 183, 4273-4283
   Abstract »    Full Text »    PDF »
Impaired Lung Dendritic Cell Migration and T Cell Stimulation Induced by Immunostimulatory Oligonucleotides Contribute to Reduced Allergic Airway Inflammation.
H. Constabel, M. V. Stankov, C. Hartwig, T. Tschernig, and G. M. N. Behrens (2009)
J. Immunol. 183, 3443-3453
   Abstract »    Full Text »    PDF »
CCL21 mediates CD4+ T-cell costimulation via a DOCK2/Rac-dependent pathway.
K. Gollmer, F. Asperti-Boursin, Y. Tanaka, K. Okkenhaug, B. Vanhaesebroeck, J. R. Peterson, Y. Fukui, E. Donnadieu, and J. V. Stein (2009)
Blood 114, 580-588
   Abstract »    Full Text »    PDF »
CXC Chemokine Ligand 12 Promotes CCR7-Dependent Naive T Cell Trafficking to Lymph Nodes and Peyer's Patches.
Z. Bai, H. Hayasaka, M. Kobayashi, W. Li, Z. Guo, M. H. Jang, A. Kondo, B.-i. Choi, Y. Iwakura, and M. Miyasaka (2009)
J. Immunol. 182, 1287-1295
   Abstract »    Full Text »    PDF »
Kinetics of Major Histocompatibility Class I Antigen Presentation in Acute Infection.
M. D. H. Lay, L. Zhang, R. M. Ribeiro, S. N. Mueller, G. T. Belz, and M. P. Davenport (2009)
J. Immunol. 182, 902-911
   Abstract »    Full Text »    PDF »
CXCL13 Is Highly Produced by Sezary Cells and Enhances Their Migratory Ability via a Synergistic Mechanism Involving CCL19 and CCL21 Chemokines.
M. C. Picchio, E. Scala, D. Pomponi, E. Caprini, M. Frontani, I. Angelucci, A. Mangoni, C. Lazzeri, M. Perez, D. Remotti, et al. (2008)
Cancer Res. 68, 7137-7146
   Abstract »    Full Text »    PDF »
Increased serum levels of the chemokine CXCL13 and up-regulation of its gene expression are distinctive features of HCV-related cryoglobulinemia and correlate with active cutaneous vasculitis.
D. Sansonno, F. A. Tucci, L. Troiani, G. Lauletta, M. Montrone, V. Conteduca, L. Sansonno, and F. Dammacco (2008)
Blood 112, 1620-1627
   Abstract »    Full Text »    PDF »
IFN-{gamma} and STAT1 Arrest Monocyte Migration and Modulate RAC/CDC42 Pathways.
Y. Hu, X. Hu, L. Boumsell, and L. B. Ivashkiv (2008)
J. Immunol. 180, 8057-8065
   Abstract »    Full Text »    PDF »
Coordination of Early Protective Immunity to Viral Infection by Regulatory T Cells.
J. M. Lund, L. Hsing, T. T. Pham, and A. Y. Rudensky (2008)
Science 320, 1220-1224
   Abstract »    Full Text »    PDF »
Ly49H+ NK Cells Migrate to and Protect Splenic White Pulp Stroma from Murine Cytomegalovirus Infection.
V. Bekiaris, O. Timoshenko, T. Z. Hou, K. Toellner, S. Shakib, F. Gaspal, F. M. McConnell, S. M. Parnell, D. Withers, C. D. Buckley, et al. (2008)
J. Immunol. 180, 6768-6776
   Abstract »    Full Text »    PDF »
Nonoverlapping Expression of IL10, IL12p40, and IFN{gamma} mRNA in the Marginal Zone and T Cell Zone of the Spleen after Antigenic Stimulation.
K. Kalies, P. Konig, Y.-M. Zhang, M. Deierling, J. Barthelmann, C. Stamm, and J. Westermann (2008)
J. Immunol. 180, 5457-5465
   Abstract »    Full Text »    PDF »
Enhancing therapeutic vaccination by blocking PD-1-mediated inhibitory signals during chronic infection.
S.-J. Ha, S. N. Mueller, E. J. Wherry, D. L. Barber, R. D. Aubert, A. H. Sharpe, G. J. Freeman, and R. Ahmed (2008)
J. Exp. Med. 205, 543-555
   Abstract »    Full Text »    PDF »
Differential Microenvironment Localization of Effector and Memory CD8 T Cells.
J. G. Dauner, I. R. Williams, and J. Jacob (2008)
J. Immunol. 180, 291-299
   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