CCR2 defines in vivo development and homing of IL-23-driven GM-CSF-producing Th17 cells

Ervin E. Kara, Duncan R. McKenzie, Cameron R. Bastow, Carly E. Gregor, Kevin A. Fenix, Abiodun D. Ogunniyi, James C. Paton, Matthias Mack, Diana R. Pombal, Cyrill Seillet, Bénédicte Dubois, Adrian Liston, Kelli P. A. MacDonald, Gabrielle T. Belz, Mark J. Smyth, Geoffrey R. Hill, Iain Comerford () and Shaun R. McColl ()
Additional contact information
Ervin E. Kara: School of Biological Sciences, University of Adelaide, Adelaide, South Australia 5005, Australia
Duncan R. McKenzie: School of Biological Sciences, University of Adelaide, Adelaide, South Australia 5005, Australia
Cameron R. Bastow: School of Biological Sciences, University of Adelaide, Adelaide, South Australia 5005, Australia
Carly E. Gregor: School of Biological Sciences, University of Adelaide, Adelaide, South Australia 5005, Australia
Kevin A. Fenix: School of Biological Sciences, University of Adelaide, Adelaide, South Australia 5005, Australia
Abiodun D. Ogunniyi: School of Biological Sciences, University of Adelaide, Adelaide, South Australia 5005, Australia
James C. Paton: School of Biological Sciences, University of Adelaide, Adelaide, South Australia 5005, Australia
Matthias Mack: University Hospital Regensburg
Diana R. Pombal: VIB and University of Leuven
Cyrill Seillet: Walter and Eliza Hall Institute of Medical Research
Bénédicte Dubois: KU-Leuven–University of Leuven
Adrian Liston: VIB and University of Leuven
Kelli P. A. MacDonald: QIMR Berghofer Medical Research Institute
Gabrielle T. Belz: Walter and Eliza Hall Institute of Medical Research
Mark J. Smyth: QIMR Berghofer Medical Research Institute
Geoffrey R. Hill: QIMR Berghofer Medical Research Institute
Iain Comerford: School of Biological Sciences, University of Adelaide, Adelaide, South Australia 5005, Australia
Shaun R. McColl: School of Biological Sciences, University of Adelaide, Adelaide, South Australia 5005, Australia

Nature Communications, 2015, vol. 6, issue 1, 1-17

Abstract: 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/IFNγ-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/IFNγ-producing Th17 cells in EAE and experimental persistent extracellular bacterial infection, and in humans. Using this signature, we identify an IL-23/IL-1/IFNγ/TNFα/T-bet/Eomesodermin-driven circuit driving GM-CSF/IFNγ-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/IFNγ-producing Th17 cells.

Date: 2015
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DOI: 10.1038/ncomms9644

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