IL-17-producing human peripheral regulatory T cells retain suppressive function.

Blood 2009 Apr 26;113(18):4240-9. Epub 2009 Jan 26.

Division of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Although implicated in antagonistic functions, both regulatory T cells (Tregs) and Th17 effector cells play an important role in controlling autoimmune pathogenesis. Paradoxically, recent studies indicate that Tregs have the capacity to produce interleukin-17 (IL-17), although the ability of these cells to retain their suppressive function remains unknown. Here we report that human Tregs within the CD4(+)CD45RA(-)CD25(high)CCR6(+)HLA-DR(-)FoxP3(+) population produce IL-17 when activated in the presence of the proinflammatory cytokines IL-1beta and IL-6, whereas IL-17 secretion was inhibited by TGFbeta. 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.

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Source
http://www.bloodjournal.org/cgi/doi/10.1182/blood-2008-10-18
Publisher Site
http://dx.doi.org/10.1182/blood-2008-10-183251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2676084PMC
April 2009
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