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IL-17 Plays an Important Role in the Development of Experimental Autoimmune Encephalomyelitis
Open accessAbstract
IL-17 is a proinflammatory cytokine that activates T cells and other immune cells to produce a variety of cytokines, chemokines, and cell adhesion molecules. This cytokine is augmented in the sera and/or tissues of patients with contact dermatitis, asthma, and rheumatoid arthritis. We previously demonstrated that IL-17 is involved in the development of autoimmune arthritis and contact, delayed, and airway hypersensitivity in mice. As the expression of IL-17 is also augmented in multiple sclerosis, we examined the involvement of this cytokine in these diseases using IL-17−/− murine disease models. We found that the development of experimental autoimmune encephalomyelitis (EAE), the rodent model of multiple sclerosis, was significantly suppressed in IL-17−/− mice; these animals exhibited delayed onset, reduced maximum severity scores, ameliorated histological changes, and early recovery. T cell sensitization against myelin oligodendrocyte glycoprotein was reduced in IL-17−/− mice upon sensitization. The major producer of IL-17 upon treatment with myelin digodendrocyte glycopritein was CD4+ T cells rather than CD8+ T cells, and adoptive transfer of IL-17−/− CD4+ T cells inefficiently induced EAE in recipient mice. Notably, IL-17-producing T cells were increased in IFN-γ−/− cells, while IFN-γ-producing cells were increased in IL-17−/− cells, suggesting that IL-17 and IFN-γ mutually regulate IFN-γ and IL-17 production. These observations indicate that IL-17 rather than IFN-γ plays a crucial role in the development of EAE.
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“a subset of CD4+ T cells that is a major contributor to the pathogenicity of several inflammatory and autoimmune conditions (9–11)”
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“inflammatory subtypes of T cells, particularly Th17 cells, are clearly deleterious in diseases such as multiple sclerosis (9–11, 24)”
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Metadata
- Authors
- Komiyama, Y., Nakae, S., Matsuki, T., Nambu, A., Ishigame, H., Kakuta, S., Sudo, K., & Iwakura, Y.
- Affiliations
- Institute of Medical Science, The University of Tokyo (JP)
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-07-01
- Volume
- 177
- Issue
- 1
- Pages
- 566-573
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1959664751
- Cited by
- 1,536
- References
- 54
- Citations by year
- 2026: 12 · 2025: 18 · 2024: 30 · 2023: 30 · 2022: 56 · 2021: 47 · 2020: 44 · 2019: 53 · 2018: 70 · 2017: 72 · 2016: 62 · 2015: 80 · 2014: 97 · 2013: 102 · 2012: 120
- FWCI
- 89.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- School of Medicine, Stanford University
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- IL-17, experimental autoimmune encephalomyelitis, multiple sclerosis, interferon-gamma, myelin oligodendrocyte glycoprotein, CD4+ T cells, T cell sensitization, adoptive transfer, cytokine regulation, autoimmune disease
- MeSH terms
- Amino Acid Sequence, Animals, Autoantibodies, Cells, Cultured, Encephalomyelitis, Autoimmune, Experimental, Glycoproteins, Interferon-gamma, Lymph Nodes, Mice, Inbred C57BL, Molecular Sequence Data, Peptide Fragments, CD4-Positive T-Lymphocytes, Up-Regulation, Mice, Knockout, Epitopes, T-Lymphocyte, Adoptive Transfer, Interleukin-17, Mice, Myelin-Oligodendrocyte Glycoprotein
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