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Science 15 October 1999:
Vol. 286. no. 5439, pp. 525 - 528
DOI: 10.1126/science.286.5439.525
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Reports

beta -Defensins: Linking Innate and Adaptive Immunity Through Dendritic and T Cell CCR6

D. Yang, 1 O. Chertov, 2 S. N. Bykovskaia, 3 Q. Chen, 1 M. J. Buffo, 3 J. Shogan, 3 M. Anderson, 4 J. M. Schröder, 5 J. M. Wang, 1 O. M. Z. Howard, 2 J. J. Oppenheim 1*

Defensins contribute to host defense by disrupting the cytoplasmic membrane of microorganisms. This report shows that human beta -defensins are also chemotactic for immature dendritic cells and memory T cells. Human beta -defensin was selectively chemotactic for cells stably transfected to express human CCR6, a chemokine receptor preferentially expressed by immature dendritic cells and memory T cells. The beta -defensin-induced chemotaxis was sensitive to pertussis toxin and inhibited by antibodies to CCR6. The binding of iodinated LARC, the chemokine ligand for CCR6, to CCR6-transfected cells was competitively displaced by beta -defensin. Thus, beta -defensins may promote adaptive immune responses by recruiting dendritic and T cells to the site of microbial invasion through interaction with CCR6.

1 Laboratory of Molecular Immunoregulation, Division of Basic Sciences,
2 Intramural Research Support Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA.
3 Allegheny University of Health Sciences, Pittsburgh, PA 15212, USA.
4 Magainin Research Institute, 5110 Campus Drive, Plymouth Meeting, PA 19642, USA.
5 Department of Dermatology, Christian Albrechts University of Kiel, Schittenhelmstrasse 7, D-24105 Kiel, Germany.
*   To whom correspondence should be addressed. E-mail: oppenhei{at}mail.ncifcrf.gov

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Paneth cells: leukocyte-like mediators of innate immunity in the intestine.
S. Keshav (2006)
J. Leukoc. Biol. 80, 500-508
   Abstract »    Full Text »    PDF »
The novel {beta}-defensin DEFB123 prevents lipopolysaccharide-mediated effects in vitro and in vivo.
D. Motzkus, S. Schulz-Maronde, A. Heitland, A. Schulz, W.-G. Forssmann, M. Jubner, and E. Maronde (2006)
FASEB J 20, 1701-1702
   Abstract »    Full Text »    PDF »
Cutting Edge: Human beta Defensin 3--A Novel Antagonist of the HIV-1 Coreceptor CXCR4.
Z. Feng, G. R. Dubyak, M. M. Lederman, and A. Weinberg (2006)
J. Immunol. 177, 782-786
   Abstract »    Full Text »    PDF »
Inhibition of {beta}-Defensin Gene Expression in Airway Epithelial Cells by Low Doses of Residual Oil Fly Ash is Mediated by Vanadium.
M. E. Klein-Patel, G. Diamond, M. Boniotto, S. Saad, and L. K. Ryan (2006)
Toxicol. Sci. 92, 115-125
   Abstract »    Full Text »    PDF »
Lipopolysaccharide-Induced IL-1beta Production by Human Uterine Macrophages Up-Regulates Uterine Epithelial Cell Expression of Human beta-Defensin 2..
P. A. Pioli, L. K. Weaver, T. M. Schaefer, J. A. Wright, C. R. Wira, and P. M. Guyre (2006)
J. Immunol. 176, 6647-6655
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The Antimicrobial/Elastase Inhibitor Elafin Regulates Lung Dendritic Cells and Adaptive Immunity.
A. Roghanian, S. E. Williams, T. A. Sheldrake, T. I. Brown, K. Oberheim, Z. Xing, S. E. M. Howie, and J.-M. Sallenave (2006)
Am. J. Respir. Cell Mol. Biol. 34, 634-642
   Abstract »    Full Text »    PDF »
Seminal plasma promotes the attraction of Langerhans cells via the secretion of CCL20 by vaginal epithelial cells: involvement in the sexual transmission of HIV.
W. Berlier, M. Cremel, H. Hamzeh, R. Levy, F. Lucht, T. Bourlet, B. Pozzetto, and O. Delezay (2006)
Hum. Reprod. 21, 1135-1142
   Abstract »    Full Text »    PDF »
Human {beta}-Defensin 2 Induces a Vigorous Cytokine Response in Peripheral Blood Mononuclear Cells..
M. Boniotto, W. J. Jordan, J. Eskdale, A. Tossi, N. Antcheva, S. Crovella, N. D. Connell, and G. Gallagher (2006)
Antimicrob. Agents Chemother. 50, 1433-1441
   Abstract »    Full Text »    PDF »
The Host Defense Peptide Beta-Defensin 1 Confers Protection against Bordetella pertussis in Newborn Piglets.
S. Elahi, R. M. Buchanan, S. Attah-Poku, H. G. G. Townsend, L. A. Babiuk, and V. Gerdts (2006)
Infect. Immun. 74, 2338-2352
   Abstract »    Full Text »    PDF »
Role of Human {beta}-defensins in HIV Infection.
A. Weinberg, M.E. Quinones-Mateu, and M.M. Lederman (2006)
Advances in Dental Research 19, 42-48
   Abstract »    Full Text »    PDF »
(C3) The Oral Epithelial Cell and First Encounters with HIV-1.
M.C. Herzberg, A. Weinberg, and S.M. Wahl (2006)
Advances in Dental Research 19, 158-166
   Abstract »    Full Text »    PDF »
NOD2/CARD15 Mediates Induction of the Antimicrobial Peptide Human Beta-defensin-2.
E. Voss, J. Wehkamp, K. Wehkamp, E. F. Stange, J. M. Schroder, and J. Harder (2006)
J. Biol. Chem. 281, 2005-2011
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The mammalian ionic environment dictates microbial susceptibility to antimicrobial defense peptides.
R. A. Dorschner, B. Lopez-Garcia, A. Peschel, D. Kraus, K. Morikawa, V. Nizet, and R. L. Gallo (2006)
FASEB J 20, 35-42
   Abstract »    Full Text »    PDF »
Why Is the Arg5-Glu13 Salt Bridge Conserved in Mammalian {alpha}-Defensins?.
Z. Wu, X. Li, E. de Leeuw, B. Ericksen, and W. Lu (2005)
J. Biol. Chem. 280, 43039-43047
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Coordinate Expression of CC Chemokine Ligand 5, Granulysin, and Perforin in CD8+ T Cells Provides a Host Defense Mechanism against Mycobacterium tuberculosis.
F. Stegelmann, M. Bastian, K. Swoboda, R. Bhat, V. Kiessler, A. M. Krensky, M. Roellinghoff, R. L. Modlin, and S. Stenger (2005)
J. Immunol. 175, 7474-7483
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Human {beta}-Defensins Suppress Human Immunodeficiency Virus Infection: Potential Role in Mucosal Protection.
L. Sun, C. M. Finnegan, T. Kish-Catalone, R. Blumenthal, P. Garzino-Demo, G. M. La Terra Maggiore, S. Berrone, C. Kleinman, Z. Wu, S. Abdelwahab, et al. (2005)
J. Virol. 79, 14318-14329
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IL-1{beta}-Mediated Proinflammatory Responses Are Inhibited by Estradiol via Down-Regulation of IL-1 Receptor Type I in Uterine Epithelial Cells.
T. M Schaefer, J. A. Wright, P. A. Pioli, and C. R. Wira (2005)
J. Immunol. 175, 6509-6516
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Up-Regulation of CC Chemokine Ligand 20 Expression in Human Airway Epithelium by IL-17 through a JAK-Independent but MEK/NF-{kappa}B-Dependent Signaling Pathway.
C.-Y. Kao, F. Huang, Y. Chen, P. Thai, S. Wachi, C. Kim, L. Tam, and R. Wu (2005)
J. Immunol. 175, 6676-6685
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Keratinocyte Production of Cathelicidin Provides Direct Activity against Bacterial Skin Pathogens.
M. H. Braff, M. Zaiou, J. Fierer, V. Nizet, and R. L. Gallo (2005)
Infect. Immun. 73, 6771-6781
   Abstract »    Full Text »    PDF »


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