Send to:

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11495-500. doi: 10.1073/pnas.1002099107. Epub 2010 Jun 7.

Identification of an IL-27/osteopontin axis in dendritic cells and its modulation by IFN-gamma limits IL-17-mediated autoimmune inflammation.

Author information

  • 1Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.


Dendritic cells (DCs) play a central role in determining the induction of T cell responses. IL-27 production by DCs favors induction of IL-10-producing regulatory T cells, whereas osteopontin (OPN) promotes pathogenic IL-17 T cell responses. The regulatory mechanisms in DCs that control these two cells types are not understood well. Here, we show that IFN-gamma induces IL-27 while inhibiting OPN expression in DCs both in vitro and in vivo and that engagement of IFN-gammaR expressed by DCs leads to suppression of IL-17 production while inducing IL-10 from T cells. DCs modified by IFN-gamma acquire IL-27-dependent regulatory function, promote IL-10-mediated T cell tolerance, and suppress autoimmune inflammation. Thus, our results identify a previously unknown pathway by which IFN-gamma limits IL-17-mediated autoimmune inflammation through differential regulation of OPN and IL-27 expression in DCs.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk