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Blood, 1 June 2005, Vol. 105, No. 11, pp. 4207-4214. Prepublished online as a Blood First Edition Paper on February 15, 2005; DOI 10.1182/blood-2004-07-2697. This Article Full Text (PDF) All Versions of this Article: 2004-07-2697v1 105/11/4207    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 Howard, O M Articles by Oppenheim, J. J Search for Related Content PubMed PubMed Citation Articles by Howard, O M Articles by Oppenheim, J. J Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 15, 2004 Accepted January 7, 2005 Autoantigens signal through chemokine receptors: uveitis antigens induce CXCR3 and CXCR5 expressing lymphocytes and immature dendritic cells to migrate O M Howard*, Hui Fang Dong, Shao Bo Su, Rachel R Caspi, Xin Chen, Paul Plotz, and Joost J Oppenheim Center for Cancer Research (CCR) Laboratory of Molecular Immunoregulation (LMI), National Cancer Institute, Frederick, MD, USA Basic Research Program, SAIC, NCI, Frederick, MD, USA Laboratory of Immunology, National Eye Institute, Bethesda, MD, USA Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Health, Bethesda, MD, USA * Corresponding author; email: howardz{at}mail.ncifcrf.gov. We tested the hypothesis that interaction between autoantigens and chemoattractant receptors may be an important step in the development of autoimmunity. The retinal autoantigens S-Antigen (S-Ag), and interphotoreceptor retinoid binding protein (IRBP) can induce autoimmune uveitis in rodent models. We evaluated the chemotactic activity of S-Ag and IRBP and found that both induced migration of human and mouse immature dendritic cells (iDCs) and lymphocytes, but not neutrophils, monocytes or mature DCs. Cross desensitization studies and single-receptor transfected cells revealed that CXCR5 and CXCR3 mediated the chemotactic effect of IRBP, while only CXCR3 was required for the chemotactic response to S-Ag. Examination of the relationships between chemoattraction and the ability to elicit pathology at the protein or peptide levels in the mouse uveitis model revealed dissociation of the capacity to induce uveitis, lymphocyte proliferation, and chemoattraction. These studies suggest that IRBP and S-Ag can initiate innate and, in sensitive individuals, adaptive immune response by attracting iDCs, T- and B-cells expressing CXCR3 and CXCR5. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Zernecke, J. Bernhagen, and C. Weber Macrophage Migration Inhibitory Factor in Cardiovascular Disease Circulation, March 25, 2008; 117(12): 1594 - 1602. [Abstract] [Full Text] [PDF] E. Csernok, M. Ai, W. L. Gross, D. Wicklein, A. Petersen, B. Lindner, P. Lamprecht, J. U. Holle, and B. Hellmich Wegener autoantigen induces maturation of dendritic cells and licenses them for Th1 priming via the protease-activated receptor-2 pathway Blood, June 1, 2006; 107(11): 4440 - 4448. [Abstract] [Full Text] [PDF]

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