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

doi:10.1038/ni1376

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

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 +7 more·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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IL-27 can inhibit the differentiation of Th17 cells.
“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]
IL-27 favors differentiation of naïve T cells to Th1 cells via IFN-γ induction.
“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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Role of Th17 cells in the pathogenesis of CNS inflammatory demyelination
Rostami, A. M., & Ćirić, B. (2013) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2013.03.002 · Cited by 275 · see citing works

Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17–producing T cells
Batten, M., Li, J., Yi, S., Kljavin, N. M., Danilenko, D. M., Lucas, S., Lee, J., de Sauvage, F. J., & Ghilardi, N. (2006) · Nature Immunology · doi:10.1038/ni1375 · Cited by 815 · see citing works
Induction of regulatory Tr1 cells and inhibition of TH17 cells by IL-27
Pot, C., Apétoh, L., Awasthi, A., & Kuchroo, V. K. (2011) · Seminars in Immunology · doi:10.1016/j.smim.2011.08.003 · Cited by 168 · see citing works
All in the family: IL-27 suppression of TH-17 cells
Colgan, J. D., & Rothman, P. B. (2006) · Nature Immunology · doi:10.1038/ni0906-899 · Cited by 53 · see citing works
IL-27 Blocks RORc Expression to Inhibit Lineage Commitment of Th17 Cells
Diveu, C., McGeachy, M. J., Boniface, K., Stumhofer, J. S., Sathe, M., Joyce-Shaikh, B., Chen, Y., Tato, C. M., McClanahan, T. K., Malefyt, R. D. W., et al. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0801162 · Cited by 332 · see citing works
Self-citation
IL‐27 controls the development of inducible regulatory T cells and Th17 cells via differential effects on STAT1
Neufert, C. F., Becker, C., Wirtz, S. J., Fantini, M. C., Weigmann, B., Galle, P. R., & Neurath, M. F. (2007) · European Journal of Immunology · doi:10.1002/eji.200636896 · Cited by 188 · see citing works

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
Health Sciences › Medicine › Oncology › 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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