Cited by 955Psoriasis: Treatment and PathogenesisT-cell and B-cell ImmunologyCytokine Signaling Pathways and Interactions

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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

Stumhofer, Jason S, Laurence, Arian, Wilson, Emma H, Huang, Elaine, Tato, Cristina M, Johnson, Leanne M, Villarino, Alejandro V, Huang, Qiulong, Yoshimura, Akihiko, Sehy, David, Saris, Christiaan J M, O'Shea, John J, Hennighausen, Lothar, Ernst, Matthias, Hunter, Christopher A·2006·Nature Immunology

DOI 10.1038/ni1376

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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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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: Stumhofer, Jason S
Laurence, Arian
Wilson, Emma H
Huang, Elaine
Tato, Cristina M
Villarino, Alejandro V
Yoshimura, Akihiko
Hennighausen, Lothar
Ernst, Matthias
Hunter, Christopher A
Venue: Nature Immunology
Publisher: Springer Science and Business Media LLC
Published: 2006-08-13
Volume: 7
Issue: 9
Pages: 937-945
ISSN: 1529-2908 (ISSN-L)
1529-2916
DOI: 10.1038/ni1376
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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Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system

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