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Prepublished online as a Blood First Edition Paper on July 24, 2003; DOI 10.1182/blood-2003-03-0946. This Article Full Text (PDF) All Versions of this Article: 2003-03-0946v1 102/10/3494    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 Barlic, J. Articles by Murphy, P. M Search for Related Content PubMed PubMed Citation Articles by Barlic, J. Articles by Murphy, P. M Social Bookmarking                   What's this? Submitted March 27, 2003 Accepted July 9, 2003 IL-15 and IL-2 oppositely regulate expression of the chemokine receptor CX3CR1 Jana Barlic, Joan M Sechler, and Philip M Murphy* Molecular Signaling Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA * Corresponding author; email: pmm{at}nih.gov. The chemokine receptor CX3CR1 is expressed in mouse blood on NK cells and on monocytes. Since IL-15 is an essential cytokine for NK cell development and maintenance, we hypothesized that it may induce CX3CR1 expression on this cell type. In contrast, we found that in primary mouse bone marrow-derived NK cells IL-15 specifically inhibited CX3CR1 protein and mRNA accumulation whereas the related cytokine IL-2 did not inhibit but instead increased CX3CR1 expression. Consistent with this, intravenous injection of a single dose of recombinant IL-15 into C57BL/6 mice decreased steady state CX3CR1 levels 24 hours after injection in freshly isolated PBMCs, splenocytes and bone marrow cells, and treatment of mouse PBMCs with IL-15 in vitro inhibited CX3CL1-induced chemotaxis. These data suggest that IL-15 may be a negative regulator of innate immunity by inhibiting CX3CR1 expression. The data also suggest that IL-15 inhibition of CX3CR1 may subvert potential cell immunotherapy strategies in which IL-15 is used to expand NK cell populations in vivo or ex vivo. Finally, our results provide additional evidence for differential signaling by IL-2 and IL-15, despite usage of common c receptor chains. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Bernardini, G. Sciume, D. Bosisio, S. Morrone, S. Sozzani, and A. Santoni CCL3 and CXCL12 regulate trafficking of mouse bone marrow NK cell subsets Blood, April 1, 2008; 111(7): 3626 - 3634. [Abstract] [Full Text] [PDF] M. G. Quaranta, A. Napolitano, M. Sanchez, L. Giordani, B. Mattioli, and M. Viora HIV-1 Nef impairs the dynamic of DC/NK crosstalk: different outcome of CD56dim and CD56bright NK cell subsets FASEB J, August 1, 2007; 21(10): 2323 - 2334. [Abstract] [Full Text] [PDF] M. V. Ramos, G. C. Fernandez, N. Patey, P. Schierloh, R. Exeni, I. Grimoldi, G. Vallejo, C. Elias-Costa, M. del Carmen Sasiain, H. Trachtman, et al. Involvement of the fractalkine pathway in the pathogenesis of childhood hemolytic uremic syndrome Blood, March 15, 2007; 109(6): 2438 - 2445. [Abstract] [Full Text] [PDF] J. Barlic, D. H. McDermott, M. N. Merrell, J. Gonzales, L. E. Via, and P. M. Murphy Interleukin (IL)-15 and IL-2 Reciprocally Regulate Expression of the Chemokine Receptor CX3CR1 through Selective NFAT1- and NFAT2-dependent Mechanisms J. Biol. Chem., November 19, 2004; 279(47): 48520 - 48534. [Abstract] [Full Text] [PDF] G. G. Neely, S. Epelman, L. L. Ma, P. Colarusso, C. J. Howlett, E. K. Amankwah, A. C. McIntyre, S. M. Robbins, and C. H. Mody Monocyte Surface-Bound IL-15 Can Function as an Activating Receptor and Participate in Reverse Signaling J. Immunol., April 1, 2004; 172(7): 4225 - 4234. [Abstract] [Full Text] [PDF]

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