Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/98145
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Type: Journal article
Title: CCR2 defines in vivo development and homing of IL-23-driven GM-CSF-producing Th17 cells
Author: Kara, E.
McKenzie, D.
Bastow, C.
Gregor, C.
Fenix, K.
Ogunniyi, A.
Paton, J.
Mack, M.
Pombal, D.
Seillet, C.
Dubois, B.
Liston, A.
Macdonald, K.
Belz, G.
Smyth, M.
Hill, G.
Comerford, I.
McColl, S.
Citation: Nature Communications, 2015; 6(1):8644-1-8644-1 7
Publisher: Nature Publishing Group
Issue Date: 2015
ISSN: 2041-1723
2041-1723
Statement of
Responsibility: 
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, Be, ne, dicte Dubois, Adrian Liston, Kelli P.A. MacDonald, Gabrielle T. Belz, Mark J. Smyth, Geoffrey R. Hill, Iain Comerford and Shaun R. McColl
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.
Keywords: Animals; Mice, Inbred C57BL; Mice, Knockout; Humans; Encephalomyelitis, Autoimmune, Experimental; Tumor Necrosis Factors; T-Box Domain Proteins; Granulocyte-Macrophage Colony-Stimulating Factor; Cell Differentiation; Interleukin-23; Receptors, CCR2; Receptors, CCR6; Interferon-gamma; Th17 Cells
Description: Published 29 October 2015
Rights: © 2015 Macmillan Publishers Limited. All rights reserved. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
RMID: 0030037922
DOI: 10.1038/ncomms9644
Appears in Collections:Molecular and Biomedical Science publications

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