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Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system
Abstract
Studies have focused on the events that influence the development of interleukin 17 (IL-17)-producing T helper cells (T(H)-17 cells) associated with autoimmunity, such as experimental autoimmune encephalitis, but relatively little is known about the cytokines that antagonize T(H)-17 cell effector responses. Here we show that IL-27 receptor-deficient mice chronically infected with Toxoplasma gondii developed severe neuroinflammation that was CD4+ T cell dependent and was associated with a prominent IL-17 response. In vitro, treatment of naive primary T cells with IL-27 suppressed the development T(H)-17 cells induced by IL-6 and transforming growth factor-beta, which was dependent on the intracellular signaling molecule STAT1 but was independent of inhibition of IL-6 signaling mediated by the suppressor protein SOCS3. Thus IL-27, a potent inhibitor of T(H)-17 cell development, may be a useful target for treating inflammatory diseases mediated by these cells.
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“In addition to favoring the differentiation of naïve T cells to Th1 cells via IFN-γ induction, IL-27 can also inhibit the differentiation of Th17 cells (57).”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [57]
In the citing paper
“In addition to favoring the differentiation of naïve T cells to Th1 cells via IFN-γ induction, IL-27 can also inhibit the differentiation of Th17 cells (57).”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [57]
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Metadata
- Authors
- Stumhofer, J. S., Laurence, A., Wilson, E. H., Huang, E., Tato, C. M., Johnson, L. M., Villarino, A. V., Huang, Q., Yoshimura, A., Sehy, D., Saris, C. J. M., O'Shea, J. J., Hennighausen, L., Ernst, M., & Hunter, C. A.
- Affiliations
- University of Pennsylvania (US)
- National Institutes of Health (US)
- Kyushu University (JP)
- Amgen (United States) (US)
- Ludwig Cancer Research (BE)
- Corresponding author
- Hunter, Christopher A
- ORCID
- Venue
- Nature Immunology
- Published
- 2006-08-13
- Volume
- 7
- Issue
- 9
- Pages
- 937-945
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W1999561404
- Cited by
- 955
- References
- 60
- Citations by year
- 2026: 5 · 2025: 17 · 2024: 20 · 2023: 25 · 2022: 25 · 2021: 27 · 2020: 43 · 2019: 28 · 2018: 31 · 2017: 37 · 2016: 41 · 2015: 38 · 2014: 48 · 2013: 73 · 2012: 67
- FWCI
- 32.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI 42334, 1-T32-AI-055428, R01AI041158, R01AI042334, AI41158, T32AI055428)
- National Institute of Neurological Disorders and Stroke (R01NS072298)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Keywords
- IL-27, IL-17, Th17 cells, neuroinflammation, Toxoplasma gondii, experimental autoimmune encephalitis, STAT1 signaling, SOCS3, interleukin-6, TGF-beta, CD4+ T cells, autoimmunity, chronic infection
- MeSH terms
- Suppressor of Cytokine Signaling 3 Protein, Animals, Central Nervous System, Encephalitis, T-Lymphocytes, Helper-Inducer, Interleukins, Lymphocyte Activation, Toxoplasma, CD4 Antigens, Interleukin-6, Toxoplasmosis, Cerebral, Receptors, Cytokine, Receptors, Interleukin, Mice, Knockout, Interleukin-17, STAT1 Transcription Factor, Suppressor of Cytokine Signaling Proteins, Mice
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