CCR2 defines in vivo development and homing of IL-23-driven GM-CSF-producing Th17 cells
- Author(s)
- Kara, EE; McKenzie, DR; Bastow, CR; Gregor, CE; Fenix, KA; Ogunniyi, AD; Paton, JC; Mack, M; Pombal, DR; Seillet, C; Dubois, B; Liston, A; MacDonald, KP; Belz, GT; Smyth, MJ; Hill, GR; Comerford, I; McColl, SR;
- Journal Title
- Nat Commun
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- NPG
- Research Division(s)
- Molecular Immunology
- PubMed ID
- 26511769
- Publisher's Version
- https://doi.org/10.1038/ncomms9644
- Open Access at Publisher's Site
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Creation Date: 2015-11-09 12:06:46
Last Modified: 2015-12-09 03:49:46