| First Author | Kara EE | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 8644 | PubMed ID | 26511769 |
| Mgi Jnum | J:227909 | Mgi Id | MGI:5703998 |
| Doi | 10.1038/ncomms9644 | Citation | Kara EE, et al. (2015) CCR2 defines in vivo development and homing of IL-23-driven GM-CSF-producing Th17 cells. Nat Commun 6:8644 |
| abstractText | IL-17-producing helper T (Th17) cells are critical for host defense against extracellular pathogens but also drive numerous autoimmune diseases. Th17 cells that differ in their inflammatory potential have been described including IL-10-producing Th17 cells that are weak inducers of inflammation and highly inflammatory, IL-23-driven, GM-CSF/IFNgamma-producing Th17 cells. However, their distinct developmental requirements, functions and trafficking mechanisms in vivo remain poorly understood. Here we identify a temporally regulated IL-23-dependent switch from CCR6 to CCR2 usage by developing Th17 cells that is critical for pathogenic Th17 cell-driven inflammation in experimental autoimmune encephalomyelitis (EAE). This switch defines a unique in vivo cell surface signature (CCR6(-)CCR2(+)) of GM-CSF/IFNgamma-producing Th17 cells in EAE and experimental persistent extracellular bacterial infection, and in humans. Using this signature, we identify an IL-23/IL-1/IFNgamma/TNFalpha/T-bet/Eomesodermin-driven circuit driving GM-CSF/IFNgamma-producing Th17 cell formation in vivo. Thus, our data identify a unique cell surface signature, trafficking mechanism and T-cell intrinsic regulators of GM-CSF/IFNgamma-producing Th17 cells. |
