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Science 307 (5707): 254-258

Copyright © 2005 by the American Association for the Advancement of Science

CX3CR1-Mediated Dendritic Cell Access to the Intestinal Lumen and Bacterial Clearance

Jan Hendrik Niess,1 Stephan Brand,1 Xiubin Gu,1 Limor Landsman,4 Steffen Jung,4,5 Beth A. McCormick,2 Jatin M. Vyas,3 Marianne Boes,6 Hidde L. Ploegh,6 James G. Fox,7 Dan R. Littman,5 Hans-Christian Reinecker1*

Abstract: Dendritic cells (DCs) and macrophages are critical to innate and adaptive immunity to the intestinal bacterial microbiota. Here, we identify a myeloid-derived mucosal DC in mice, which populates the entire lamina propria of the small intestine. Lamina propria DCs were found to depend on the chemokine receptor CX3CR1 to form transepithelial dendrites, which enable the cells to directly sample luminal antigens. CX3CR1 was also found to control the clearance of entero-invasive pathogens by DCs. Thus, CX3CR1-dependent processes, which control host interactions of specialized DCs with commensal and pathogenic bacteria, may regulate immunological tolerance and inflammation.

1 Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
2 Department of Pediatric Gastroenterology, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
3 Division of Infectious Diseases and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
4 Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
5 Molecular Pathogenesis Program, Howard Hughes Medical Institute, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.
6 Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
7 Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Building 16-825A, Cambridge, MA 02139, USA.

* To whom correspondence should be addressed. E-mail: hans-christian_reinecker{at}

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S. Vaishnava, C. L. Behrendt, A. S. Ismail, L. Eckmann, and L. V. Hooper (2008)
PNAS 105, 20858-20863
   Abstract »    Full Text »    PDF »
Polymorphism in the Microglial Cell-Mobilizing CX3CR1 Gene Is Associated With Survival in Patients With Glioblastoma.
M. Rodero, Y. Marie, M. Coudert, E. Blondet, K. Mokhtari, A. Rousseau, W. Raoul, C. Carpentier, F. Sennlaub, P. Deterre, et al. (2008)
J. Clin. Oncol. 26, 5957-5964
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CX3CL1/fractalkine is released from apoptotic lymphocytes to stimulate macrophage chemotaxis.
L. A. Truman, C. A. Ford, M. Pasikowska, J. D. Pound, S. J. Wilkinson, I. E. Dumitriu, L. Melville, L. A. Melrose, C. A. Ogden, R. Nibbs, et al. (2008)
Blood 112, 5026-5036
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Lymph-migrating, tissue-derived dendritic cells are minor constituents within steady-state lymph nodes.
C. Jakubzick, M. Bogunovic, A. J. Bonito, E. L. Kuan, M. Merad, and G. J. Randolph (2008)
J. Exp. Med. 205, 2839-2850
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Goblet Cell-Derived Resistin-Like Molecule {beta} Augments CD4+ T Cell Production of IFN-{gamma} and Infection-Induced Intestinal Inflammation.
M. G. Nair, K. J. Guild, Y. Du, C. Zaph, G. D. Yancopoulos, D. M. Valenzuela, A. Murphy, S. Stevens, M. Karow, and D. Artis (2008)
J. Immunol. 181, 4709-4715
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In Vivo Visualization of Dendritic Cells, Macrophages, and Microglial Cells Responding to Laser-Induced Damage in the Fundus of the Eye.
N. Eter, D. R. Engel, L. Meyer, H.-M. Helb, F. Roth, J. Maurer, F. G. Holz, and C. Kurts (2008)
Invest. Ophthalmol. Vis. Sci. 49, 3649-3658
   Abstract »    Full Text »    PDF »
Scavenging roles of chemokine receptors: chemokine receptor deficiency is associated with increased levels of ligand in circulation and tissues.
A. E. Cardona, M. E. Sasse, L. Liu, S. M. Cardona, M. Mizutani, C. Savarin, T. Hu, and R. M. Ransohoff (2008)
Blood 112, 256-263
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Guanylyl Cyclase C-Induced Immunotherapeutic Responses Opposing Tumor Metastases Without Autoimmunity.
A. E. Snook, B. J. Stafford, P. Li, G. Tan, L. Huang, R. Birbe, S. Schulz, M. J. Schnell, M. Thakur, J. L. Rothstein, et al. (2008)
J Natl Cancer Inst 100, 950-961
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A Novel Adenovirus Expressing Flt3 Ligand Enhances Mucosal Immunity by Inducing Mature Nasopharyngeal-Associated Lymphoreticular Tissue Dendritic Cell Migration.
S. Sekine, K. Kataoka, Y. Fukuyama, Y. Adachi, J. Davydova, M. Yamamoto, R. Kobayashi, K. Fujihashi, H. Suzuki, D. T. Curiel, et al. (2008)
J. Immunol. 180, 8126-8134
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Immunology of the gut and liver: a love/hate relationship.
D H Adams, B Eksteen, and S M Curbishley (2008)
Gut 57, 838-848
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