Kara, Ervin E. and McKenzie, Duncan R. and Bastow, Cameron R. and Gregor, Carly E. and Fenix, Kevin A. and Ogunniyi, Abiodun D. and Paton, James C. and Mack, Matthias and Pombal, Diana R. and Seillet, Cyrill and Dubois, Benedicte and Liston, Adrian and MacDonald, Kelli P. A. and Belz, Gabrielle T. and Smyth, Mark J. and Hill, Geoffrey R. and Comerford, Iain and McColl, Shaun R. (2015) CCR2 defines in vivo development and homing of IL-23-driven GM-CSF-producing Th17 cells. NATURE COMMUNICATIONS, 6: 8644. ISSN 2041-1723,
Full text not available from this repository. (Request a copy)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/IFN gamma-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/IFN gamma-producing Th17 cells in EAE and experimental persistent extracellular bacterial infection, and in humans. Using this signature, we identify an IL-23/1L-1/IFNV INF alpha/T-bet/Eomesodermin-driven circuit driving GM-CSF/IFN gamma-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/IFN gamma-producing Th17 cells.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; TUMOR-NECROSIS-FACTOR; IL-17-PRODUCING T-CELLS; PATHOGENIC T(H)17 CELLS; CHEMOKINE RECEPTOR 2; ROR-GAMMA-T; IFN-GAMMA; MULTIPLE-SCLEROSIS; IMMUNE-RESPONSES; CUTTING EDGE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Jun 2019 06:17 |
| Last Modified: | 07 Jun 2019 06:17 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4792 |
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