Suppression of autoimmune inflammation of the central nervous system by interleukin 10 secreted by interleukin 27–stimulated T cells
Abstract
Excessive inflammation occurs during infection and autoimmunity in mice lacking the alpha-subunit of the interleukin 27 (IL-27) receptor. The molecular mechanisms underlying this increased inflammation are incompletely understood. Here we report that IL-27 upregulated IL-10 in effector T cells that produced interferon-gamma and expressed the transcription factor T-bet but did not express the transcription factor Foxp3. These IFN-gamma+T-bet+Foxp3- cells resembled effector T cells that have been identified as the main source of host-protective IL-10 during inflammation. IL-27-induced production of IL-10 was associated with less secretion of IL-17, and exogenous IL-27 reduced the severity of adoptively transferred experimental autoimmune encephalomyelitis by a mechanism dependent on IL-10. Our data show that IL-27-induced production of IL-10 by effector T cells contributes to the immunomodulatory function of IL-27.
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Ustekinumab, an inhibitor of p40 targeting IL-23 and IL-12, was first shown to be efficacious in treating psoriasis.
“After the identification of the IL-23/IL-17 axis as an important mediator of pathogenesis in preclinical models, ustekinumab, an inhibitor of p40 targeting both IL-23 and IL-12, was first shown to be efficacious in treating psoriasis [136].”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [136]
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- Authors
- Fitzgerald, D. C., Zhang, G.-X., El-Behi, M., Fonseca-Kelly, Z., Li, H., Yu, S., Saris, C. J. M., Gran, B., Ciric, B., & Rostami, A.
- Affiliations
- Thomas Jefferson University (US)
- Amgen (United States) (US)
- Corresponding author
- Rostami, Abdolmohamad
- ORCID
- Venue
- Nature Immunology
- Published
- 2007-11-11
- Volume
- 8
- Issue
- 12
- Pages
- 1372-1379
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2067640086
- Cited by
- 529
- References
- 3
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 12 · 2023: 14 · 2022: 15 · 2021: 19 · 2020: 26 · 2019: 23 · 2018: 14 · 2017: 25 · 2016: 30 · 2015: 33 · 2014: 32 · 2013: 43 · 2012: 39
- FWCI
- 18.31
- Type
- journal article
- Language
- en
- Update notices
- erratum (2008-01-01)
- Open access
- closed
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Funders
- National Institutes of Health (5r01ai061818-05)
- National Institute of Allergy and Infectious Diseases (5R01AI061818)
- National Institute of Neurological Disorders and Stroke (5R01NS0467892)
- 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 › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- IL-27, IL-10, experimental autoimmune encephalomyelitis, autoimmune inflammation, central nervous system autoimmunity, IL-27 receptor alpha, effector T cells, interferon-gamma, T-bet, Foxp3, IL-17, immunomodulation, adoptive transfer
- MeSH terms
- Animals, Central Nervous System Diseases, Encephalomyelitis, Autoimmune, Experimental, Inflammation, Lymphocyte Activation, T-Lymphocytes, Autoimmunity, Interleukin-10, Interleukin-17, T-Lymphocytes, Regulatory, Mice
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