HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Huang, D. Articles by Ransohoff, R. M. Search for Related Content PubMed PubMed Citation Articles by Huang, D. Articles by Ransohoff, R. M.

The neuronal chemokine CX3CL1/fractalkine selectively recruits NK cells that modify experimental autoimmune encephalomyelitis within the central nervous system

DeRen Huang^*,1, Fu-Dong Shi^,1, Steffen Jung, Gary C. Pien, Jintang Wang^*, Thais P. Salazar-Mather, Toby T. He^*, Jennifer T. Weaver^*, Hans-Gustaf Ljunggren^||, Christine A. Biron, Dan R. Littman and Richard M. Ransohoff^*,2

^* Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Ohio, USA;

Barrow Neurological Institute, Phoenix, Arizona, USA;

Skirball Institute of Biomolecular Medicine and Howard Hughes Medical Institute, New York University Medical Center, New York, New York, USA;

Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, Rhode Island, USA; and

^|| Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden

²Correspondence: Neuroinflammation Research Center, Department of Neurosciences NC30, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195, USA. E-mail: ransohr{at}ccf.org

Leukocyte trafficking to the central nervous system (CNS), regulated in part by chemokines, determines severity of the demyelinating diseases multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). To examine chemokine receptor CX3CR1 in EAE, we studied CX3CR1^GFP/GFP mice, in which CX3CR1 targeting by insertion of Green Fluorescent Protein (GFP) allowed tracking of CX3CR1+ cells in CX3CR1^+/GFP animals and cells destined to express CX3CR1 in CX3CR1^GFP/GFP knockouts. NK cells were markedly reduced in the inflamed CNS of CX3CR1-deficient mice with EAE, whereas recruitment of T cells, NKT cells and monocyte/macrophages to the CNS during EAE did not require CX3CR1. Impaired recruitment of NK cells in CX3CR1^GFP/GFP mice was associated with increased EAE-related mortality, nonremitting spastic paraplegia and hemorrhagic inflammatory lesions. The absence of CD1d did not affect the severity of EAE in CX3CR1^GFP/GFP mice, arguing against a role for NKT cells. Accumulation of NK cells in livers of wild-type (WT) and CX3CR1^GFP/GFP mice with cytomegalovirus hepatitis was equivalent, indicating that CX3CL1 mediated chemoattraction of NK cells was relatively specific for the CNS. These results are the first to define a chemokine that governs NK cell migration to the CNS, and the findings suggest novel therapeutic manipulation of CX3CR1+ NK cells. Huang, D., Shi, F.-D., Jung, S., Pien, G. C., Wang, J., Salazar-Mather, T. P., He, T. T., Weaver, J. T., Ljunggren, H. G., Biron, C. A., Littman, D. R., Ransohoff, R. M.

Key Words: autoimmune disease • chemokine • chemokine receptor • NK • T cell

This article has been cited by other articles:

				J. D. Lunemann and C. Munz Do natural killer cells accelerate or prevent autoimmunity in multiple sclerosis? Brain, July 1, 2008; 131(7): 1681 - 1683. [Full Text] [PDF]

				C. Lauro, S. Di Angelantonio, R. Cipriani, F. Sobrero, L. Antonilli, V. Brusadin, D. Ragozzino, and C. Limatola Activity of Adenosine Receptors Type 1 Is Required for CX3CL1-Mediated Neuroprotection and Neuromodulation in Hippocampal Neurons J. Immunol., June 1, 2008; 180(11): 7590 - 7596. [Abstract] [Full Text] [PDF]

				J. Kezic, H. Xu, H. R. Chinnery, C. C. Murphy, and P. G. McMenamin Retinal Microglia and Uveal Tract Dendritic Cells and Macrophages Are Not CX3CR1 Dependent in Their Recruitment and Distribution in the Young Mouse Eye Invest. Ophthalmol. Vis. Sci., April 1, 2008; 49(4): 1599 - 1608. [Abstract] [Full Text] [PDF]

				R. Winkler-Pickett, H. A. Young, J. M. Cherry, J. Diehl, J. Wine, T. Back, W. E. Bere, A. T. Mason, and J. R. Ortaldo In Vivo Regulation of Experimental Autoimmune Encephalomyelitis by NK Cells: Alteration of Primary Adaptive Responses J. Immunol., April 1, 2008; 180(7): 4495 - 4506. [Abstract] [Full Text] [PDF]

				T. Chitnis, J. Imitola, Y. Wang, W. Elyaman, P. Chawla, M. Sharuk, K. Raddassi, R. T. Bronson, and S. J. Khoury Elevated Neuronal Expression of CD200 Protects Wlds Mice from Inflammation-Mediated Neurodegeneration Am. J. Pathol., May 1, 2007; 170(5): 1695 - 1712. [Abstract] [Full Text] [PDF]