Cited by 739Psoriasis: Treatment and PathogenesisCytokine Signaling Pathways and InteractionsT-cell and B-cell Immunology

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Regulation of inflammatory responses by IL-17F

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Yang, Xuexian O., Chang, Seon Hee, Park, Heon, Nurieva, Roza, Shah, Bhavin, Acero, Luis, Wang, Yi-Hong, Schluns, Kimberly S., Broaddus, Russell R., Zhu, Zhou, Dong, Chen·2008·The Journal of Experimental Medicine

DOI 10.1084/jem.20071978PMC PMC2373839

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Abstract

Although interleukin (IL) 17 has been extensively characterized, the function of IL-17F, which has an expression pattern regulated similarly to IL-17, is poorly understood. We show that like IL-17, IL-17F regulates proinflammatory gene expression in vitro, and this requires IL-17 receptor A, tumor necrosis factor receptor–associated factor 6, and Act1. In vivo, overexpression of IL-17F in lung epithelium led to infiltration of lymphocytes and macrophages and mucus hyperplasia, similar to observations made in IL-17 transgenic mice. To further understand the function of IL-17F, we generated and analyzed mice deficient in IL-17F or IL-17. IL-17, but not IL-17F, was required for the initiation of experimental autoimmune encephalomyelitis. Mice deficient in IL-17F, but not IL-17, had defective airway neutrophilia in response to allergen challenge. Moreover, in an asthma model, although IL-17 deficiency reduced T helper type 2 responses, IL-17F–deficient mice displayed enhanced type 2 cytokine production and eosinophil function. In addition, IL-17F deficiency resulted in reduced colitis caused by dextran sulfate sodium, whereas IL-17 knockout mice developed more severe disease. Our results thus demonstrate that IL-17F is an important regulator of inflammatory responses that seems to function differently than IL-17 in immune responses and diseases.

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Authors: Yang, X. O., Chang, S. H., Park, H., Nurieva, R., Shah, B., Acero, L., Wang, Y.-H., Schluns, K. S., Broaddus, R. R., Zhu, Z., & Dong, C.
Affiliations: The University of Texas MD Anderson Cancer Center (US)
1Department of Immunology
University of Washington (US)
Johns Hopkins University (US)
ORCID: Yang, Xuexian O.
Chang, Seon Hee
Park, Heon
Nurieva, Roza
Schluns, Kimberly S.
Broaddus, Russell R.
Zhu, Zhou
Dong, Chen
Venue: The Journal of Experimental Medicine
Publisher: Rockefeller University Press
Published: 2008-04-14
Volume: 205
Issue: 5
Pages: 1063-1075
ISSN: 0022-1007 (ISSN-L)
1540-9538
DOI: 10.1084/jem.20071978
PMC: PMC2373839
OpenAlex: W2110264653
Cited by: 739
References: 47
Citations by year: 2026: 6 · 2025: 14 · 2024: 18 · 2023: 27 · 2022: 40 · 2021: 31 · 2020: 33 · 2019: 27 · 2018: 38 · 2017: 45 · 2016: 39 · 2015: 54 · 2014: 56 · 2013: 56 · 2012: 54
FWCI: 28.07
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: cc-by-nc-sa
Locations: The Journal of Experimental Medicine (publishedVersion)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords: IL-17F, IL-17, inflammation, IL-17 receptor A, TRAF6, Act1, pro-inflammatory gene expression, lung epithelium, experimental autoimmune encephalomyelitis, airway neutrophilia, allergen challenge, asthma, Th2 immune response, eosinophils, colitis, dextran sulfate
MeSH terms: Animals, Cell Line, Fibroblasts, Homeostasis, Inflammation, Lymphocyte Activation, Mice, Transgenic, T-Lymphocytes, Transfection, CD4-Positive T-Lymphocytes, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Interleukin-17, Mice

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Regulation of inflammatory responses by IL-17F

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