CCR2 defines in vivo development and homing of IL-23-driven GM-CSF-producing Th17 cells
Open accessAbstract
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.
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Highly inflammatory Th17 cells in the CNS can switch their surface signature from CCR6 into CCR2.
“Highly inflammatory Th17 cells in the CNS can switch their surface signature from C–C chemokine receptor (CCR) 6 into CCR2 [64].”
From Chronic stress-induced depression requires the recruitment of peripheral Th17 cells into the brain (2022) · cites this paper as [64]
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References 67 · Cited by 136
- Authors
- Kara, E. E., McKenzie, D. R., Bastow, C. R., Gregor, C. E., Fenix, K. A., Ogunniyi, A. D., Paton, J. C., Mack, M., Pombal, D. R., Seillet, C., Dubois, B., Liston, A., MacDonald, K. P. A., Belz, G. T., Smyth, M. J., Hill, G. R., Comerford, I., & McColl, S. R.
- Affiliations
- The University of Adelaide (AU)
- University Hospital Regensburg (DE)
- VIB-KU Leuven Center for Microbiology (BE)
- KU Leuven (BE)
- QIMR Berghofer Medical Research Institute (AU)
- The University of Melbourne (AU)
- The University of Queensland (AU)
- Corresponding author
- Comerford, Iain
- McColl, Shaun R.
- ORCID
- Venue
- Nature Communications
- Published
- 2015-10-29
- Volume
- 6
- Issue
- 1
- Pages
- 8644-8644
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4639903
- OpenAlex
- W1890836614
- Cited by
- 136
- References
- 67
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 5 · 2023: 13 · 2022: 18 · 2021: 15 · 2020: 17 · 2019: 8 · 2018: 13 · 2017: 18 · 2016: 12
- FWCI
- 7.05
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Regensburg Publication Server (University of Regensburg) (acceptedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- Lirias (KU Leuven) (submittedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion, cc-by)
- UniSA Research Outputs Repository (University of South Australia) (submittedVersion, cc-by)
- Funders
- QIMR Berghofer Medical Research Institute
- Multiple Sclerosis Australia
- University of Adelaide
- Curtin University of Technology
- Royal Adelaide Hospital
- Medical Research Council
- National Health and Medical Research Council (1066781, 1078671)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Keywords
- Th17 cells, IL-23, GM-CSF, interferon-gamma, CCR2, CCR6, T cell homing, experimental autoimmune encephalomyelitis, T-bet, Eomesodermin, interleukin-1, TNF-α, Th17 cell differentiation
- MeSH terms
- T-bet Transcription Factor, Animals, Cell Differentiation, Encephalomyelitis, Autoimmune, Experimental, Humans, Interferon-gamma, Mice, Inbred C57BL, Granulocyte-Macrophage Colony-Stimulating Factor, Mice, Knockout, T-Box Domain Proteins, Tumor Necrosis Factors, Interleukin-23, Receptors, CCR2, Receptors, CCR6, Th17 Cells
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