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Blood, 30 April 2009, Vol. 113, No. 18, pp. 4240-4249. Prepublished online as a Blood First Edition Paper on January 26, 2009; DOI 10.1182/blood-2008-10-183251. This Article Full Text (PDF) All Versions of this Article: blood-2008-10-183251v1 113/18/4240    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 Beriou, G. Articles by Hafler, D. A. Search for Related Content PubMed PubMed Citation Articles by Beriou, G. Articles by Hafler, D. A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 8, 2008 Accepted January 12, 2009 IL-17 producing human peripheral regulatory T cells retain suppressive function Gaelle Beriou, Cristina M. Costantino, Charles W. Ashley, Li Yang, Vijay K. Kuchroo, Clare Baecher-Allan*, and David A. Hafler Division of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States * Corresponding author; email: callan{at}rics.bwh.harvard.edu. Although implicated in antagonistic functions, both regulatory T cells and Th17 effector cells play an important role in controlling autoimmune pathogenesis. Paradoxically, recent studies indicate that Tregs have the capacity to produce IL-17, although the ability of these cells to retain their suppressive function remains unknown. Here we report that human Tregs within the CD4+CD45RAnegCD25highCCR6+HLA-DRnegFoxP3+ population produce IL-17 when activated in the presence of the pro-inflammatory cytokines IL-1 and IL-6, while IL-17 secretion was inhibited by TGF. In order to assess the ability of a single Treg to secrete IL-17 and to suppress in vitro immune function, we isolated clones from this population. We found that IL-17+/FoxP3+ Treg clones retain suppressive function and exhibit the plasticity to secrete IL-17 or suppress depending on the nature of the stimulus provided. IL-17 production by these Treg clones was accompanied by sustained FoxP3 expression and concomitant, but reversible, loss of suppressive activity. Our data demonstrate that at the single cell level a subset of in vitro suppressive FoxP3+ cells can be driven to secrete IL-17 under inflammatory conditions. These findings suggest a new mechanism by which inflammation can drive Tregs to secrete IL-17, thereby dampening suppression and promoting an inflammatory milieu. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. M. Fletcher, R. Lonergan, L. Costelloe, K. Kinsella, B. Moran, C. O'Farrelly, N. Tubridy, and K. H. G. Mills CD39+Foxp3+ Regulatory T Cells Suppress Pathogenic Th17 Cells and Are Impaired in Multiple Sclerosis J. Immunol., December 1, 2009; 183(11): 7602 - 7610. [Abstract] [Full Text] [PDF] B. C.-H. Kwan, L.-S. Tam, K.-B. Lai, F. M.-M. Lai, E. K.-M. Li, G. Wang, K.-M. Chow, P. K.-T. Li, and C.-C. Szeto The gene expression of type 17 T-helper cell-related cytokines in the urinary sediment of patients with systemic lupus erythematosus Rheumatology, December 1, 2009; 48(12): 1491 - 1497. [Abstract] [Full Text] [PDF] 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] R. Wang, L. Kozhaya, F. Mercer, A. Khaitan, H. Fujii, and D. Unutmaz Expression of GARP selectively identifies activated human FOXP3+ regulatory T cells PNAS, August 11, 2009; 106(32): 13439 - 13444. [Abstract] [Full Text] [PDF]

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