A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17
Abstract
Interleukin 17 (IL-17) has been linked to autoimmune diseases, although its regulation and function have remained unclear. Here we have evaluated in vitro and in vivo the requirements for the differentiation of naive CD4 T cells into effector T helper cells that produce IL-17. This process required the costimulatory molecules CD28 and ICOS but was independent of the cytokines and transcription factors required for T helper type 1 or type 2 differentiation. Furthermore, both IL-4 and interferon-gamma negatively regulated T helper cell production of IL-17 in the effector phase. In vivo, antibody to IL-17 inhibited chemokine expression in the brain during experimental autoimmune encephalomyelitis, whereas overexpression of IL-17 in lung epithelium caused chemokine production and leukocyte infiltration. Thus, IL-17 expression characterizes a unique T helper lineage that regulates tissue inflammation.
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IL-23-induced IL-17 expression in activated T cells requires prior IL-23R induction through STAT3 signaling initiated by IL-6 or IL-21 and amplified by IL-23.
“While IL-23 induced IL-17 expression in activated T cells, this required prior induction of IL-23R through STAT3-mediated signaling initiated by IL-6 or IL-21 and amplified by IL-23 itself.”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [9]
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References 40 · Cited by 4,265
- Authors
- Park, H., Li, Z., Yang, X. O., Chang, S. H., Nurieva, R., Wang, Y.-H., Wang, Y., Hood, L., Zhu, Z., Tian, Q., & Dong, C.
- Affiliations
- University of Washington (US)
- The University of Texas MD Anderson Cancer Center (US)
- Institute for Systems Biology (US)
- Johns Hopkins University (US)
- Corresponding author
- Dong, Chen
- ORCID
- Venue
- Nature Immunology
- Published
- 2005-10-02
- Volume
- 6
- Issue
- 11
- Pages
- 1133-1141
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W1987628377
- Cited by
- 4,265
- References
- 40
- Citations by year
- 2026: 48 · 2025: 99 · 2024: 133 · 2023: 124 · 2022: 150 · 2021: 146 · 2020: 156 · 2019: 131 · 2018: 150 · 2017: 189 · 2016: 167 · 2015: 237 · 2014: 261 · 2013: 268 · 2012: 301
- FWCI
- 81.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI050761, R01AI050746)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR050772)
- 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 › IL-33, ST2, and ILC Pathways
- Keywords
- IL-17, CD4+ T cells, T helper cell differentiation, CD28, ICOS, costimulation, IL-4, interferon-gamma, experimental autoimmune encephalomyelitis, chemokine expression, leukocyte infiltration, tissue inflammation, autoimmune disease, lung epithelium
- MeSH terms
- Animals, Antigens, Differentiation, T-Lymphocyte, Cell Differentiation, Gene Expression Regulation, T-Lymphocytes, Helper-Inducer, Inflammation, Lung, Mice, Transgenic, Mutation, Pneumonia, CD4-Positive T-Lymphocytes, CD28 Antigens, Chemokines, Cell Lineage, Interleukin-17, Mice, Rats, Inducible T-Cell Co-Stimulator Protein
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