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) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Murugaiyan, G. Articles by Weiner, H. L. Search for Related Content PubMed PubMed Citation Articles by Murugaiyan, G. Articles by Weiner, H. L.

Increased Osteopontin Expression in Dendritic Cells Amplifies IL-17 Production by CD4⁺ T Cells in Experimental Autoimmune Encephalomyelitis and in Multiple Sclerosis¹

Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115

Osteopontin (Opn) is a broadly expressed pleiotropic cytokine, and has been shown to play an important role in various autoimmune diseases, including multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). It is reported that Opn exacerbates EAE by skewing T cell differentiation toward IFN--producing Th1 cells. Opn expression in dendritic cells (DCs) and its role in IL-17 induction from T cells during EAE or MS are unknown. We found that during EAE, Opn expression is elevated in DCs both in the periphery and in the CNS. There was increased expression of Opn receptor on T cells, and Opn induced IL-17 production by CD4⁺ T cells via the β₃ integrin receptor and Opn inhibited IL-10 production via the CD44 receptor. Furthermore, anti-Opn treatment reduced clinical severity of EAE by reducing IL-17 production. Anti-Opn was also effective in reducing clinical severity of EAE when given after the appearance of clinical symptoms. Analogous to EAE, in subjects with MS, we found increased expression of Opn in DCs and increased expression of the Opn receptors CD44, β₃, and _v on T cells. Furthermore, Opn-stimulated CD4⁺ T cells from MS patients produced significantly higher amounts of IL-17. Our results demonstrate a role for DC-produced Opn both in EAE and MS that is linked to the production of IL-17.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health grants (NS038037, AI043458, and NS23132) and the Nancy Davis Foundation. A.M. was supported by the National Research Service Award fellowship (Grant F32AI075761) from the National Institute of Allergy and Infectious Diseases. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health.

² G.M. and A.M. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Howard L. Weiner, Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, HIM 720, 77 Avenue Louis Pasteur, Boston, MA 02115. E-mail address: hweiner{at}rics.bwh.harvard.edu

⁴ Abbreviations used in this paper: Opn, osteopontin; DC, dendritic cell; EAE, experimental autoimmune encephalomyelitis; LN, lymph node; MOG, myelin oligodendrocyte glycoprotein; MS, multiple sclerosis; WT, wild type.

This article has been cited by other articles:

				G. Murugaiyan and B. Saha Protumor vs Antitumor Functions of IL-17 J. Immunol., October 1, 2009; 183(7): 4169 - 4175. [Abstract] [Full Text] [PDF]

				M. Han and L Steinman Systems biology for identification of molecular networks in multiple sclerosis Multiple Sclerosis, May 1, 2009; 15(5): 529 - 530. [PDF]

				A. Awasthi and V. K. Kuchroo Th17 cells: from precursors to players in inflammation and infection Int. Immunol., May 1, 2009; 21(5): 489 - 498. [Abstract] [Full Text] [PDF]