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Fate-Mapping of GM-CSF Expression Identifies a Discrete Subset of Inflammation-Driving T Helper Cells Regulated by Cytokines IL-23 and IL-1β
Open accessAbstract
Pathogenic lymphocytes initiate the development of chronic inflammatory diseases. The cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) (encoded by Csf2) is a key communicator between pathogenic lymphocytes and tissue-invading inflammatory phagocytes. However, the molecular properties of GM-CSF-producing cells and the mode of Csf2 regulation in vivo remain unclear. To systematically study and manipulate GM-CSF+ cells and their progeny in vivo, we generated a fate-map and reporter of GM-CSF expression mouse strain (FROG). We mapped the phenotypic and functional profile of auto-aggressive T helper (Th) cells during neuroinflammation and identified the signature and pathogenic memory of a discrete encephalitogenic Th subset. These cells required interleukin-23 receptor (IL-23R) and IL-1R but not IL-6R signaling for their maintenance and pathogenicity. Specific ablation of this subset interrupted the inflammatory cascade, despite the unperturbed tissue accumulation of other Th subsets (e.g., Th1 and Th17), highlighting that GM-CSF expression not only marks pathogenic Th cells, but that this subset mediates immunopathology and tissue destruction.
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Metadata
- Authors
- Komuczki, J., Tuzlak, S., Friebel, E., Hartwig, T., Spath, S., Rosenstiel, P., Waisman, A., Opitz, L., Oukka, M., Schreiner, B., Pelczar, P., & Becher, B.
- Affiliations
- University of Zurich (CH)
- Christian-Albrechts-Universität zu Kiel (DE)
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Seattle Children's Research Institute (US)
- Corresponding author
- Becher, Burkhard
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2019-05
- Volume
- 50
- Issue
- 5
- Pages
- 1289-1304.e6
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2944572075
- Cited by
- 201
- References
- 99
- Citations by year
- 2026: 18 · 2025: 27 · 2024: 22 · 2023: 24 · 2022: 27 · 2021: 36 · 2020: 34 · 2019: 12
- FWCI
- 10.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Swiss National Science Foundation (316030_150768, 310030_146130)
- European Community FP7 (602239)
- University Research Priority Program
- Austrian Academy of Science
- DFG Cluster of Excellence Inflammation at Interfaces
- EU H2020 (SYSCID (#733100))
- DFG (CRC/TR 128)
- Hertie Stiftung
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Keywords
- GM-CSF, T helper cells, neuroinflammation, multiple sclerosis, encephalitogenic T cells, IL-23, IL-1β, IL23R, IL-1 receptor, fate mapping, immunopathology, Th1 cells, Th17 cells
- MeSH terms
- Receptors, CXCR6, Animals, Female, Inflammation, Interferon-gamma, Male, Mice, Inbred C57BL, Tumor Necrosis Factor-alpha, Granulocyte-Macrophage Colony-Stimulating Factor, Receptors, Interleukin, Mice, Knockout, Th1 Cells, Mice, Receptors, Interleukin-1 Type I, Interleukin-1beta, Interleukin-23 Subunit p19, Th17 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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