ArticleScientific reports2017
The human IL-17A/F heterodimer: a two-faced cytokine with unique receptor recognition properties.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 95 citations in OpenAlex.
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- Olive (Olea europaea) phenolics for the control of psoriasis via targeting SMYD2 and IL-17A protein-protein interaction networks.Journal of natural medicines · 2026Article
- Progress in Designing Cytokine Antagonist Antibodies for Cancer Therapy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Impact of Curcumin on the IL-17A-Mediated p53-Fibrinolytic System: Mouse Proteomics and Integrated Human Fibrosis scRNAseq Insights.Inflammation · 2025Article
- Understanding the role of immune-mediated inflammatory disease related cytokines interleukin 17 and 23 in pregnancy: A systematic review.Journal of translational autoimmunity · 2025Review
- Identification and Validation of Hub Genes in Hidradenitis Suppurativa.Clinical, cosmetic and investigational dermatology · 2025Article
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- Colitis induced by IL-17A-inhibitors.Clinical journal of gastroenterology · 2024Article
- Structure and function of therapeutic antibodies approved by the US FDA in 2023.Antibody therapeutics · 2024Review
- Deciphering the role of IL17RA in psoriasis and chronic mucocutaneous candidiasis: shared pathways and distinct manifestations.Frontiers in immunology · 2024Article
- The Role of Interleukins in HBV Infection: A Narrative Review.Journal of personalized medicine · 2023Review
- Differential effects of interleukin-17A and 17F on cell interactions between immune cells and stromal cells from synovium or skin.Scientific reports · 2023Article
- IL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine Trypanosoma brucei infection.Nature communications · 2023Article
- Modulation of IL-17 backbone dynamics reduces receptor affinity and reveals a new inhibitory mechanism.Chemical science · 2023Article
- Interaction of Interleukin-17A with a Th2 Response in a Mouse Model of Allergic Airway Inflammation.Cells · 2023Article
- Pathogenic Role of IL-17 and Therapeutic Targeting of IL-17F in Psoriatic Arthritis and Spondyloarthropathies.International journal of molecular sciences · 2023Review
- The IL-17 pathway as a target in giant cell arteritis.Frontiers in immunology · 2023Review
- The role of Th-17 cells and IL-17 in the metastatic spread of breast cancer: As a means of prognosis and therapeutic target.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
IL-17A and IL-17F are prominent members of the IL-17 family of cytokines that regulates both innate and adaptive immunity. IL-17A has been implicated in chronic inflammatory and autoimmune diseases, and anti-IL-17A antibodies have shown remarkable clinical efficacy in psoriasis and psoriatic arthritis patients. IL-17A and IL-17F are homodimeric cytokines that can also form the IL-17A/F heterodimer whose precise role in health and disease remains elusive. All three cytokines signal through the assembly of a ternary complex with the IL-17RA and IL-17RC receptors. Here we report the X-ray analysis of the human IL-17A/F heterodimer that reveals a two-faced cytokine closely mimicking IL-17A as well as IL-17F. We also present the crystal structure of its complex with the IL-17RA receptor. Unexpectedly in view of the much higher affinity of this receptor toward IL-17A, we find that IL-17RA is bound to the "F-face" of the heterodimer in the crystal. Using site-directed mutagenesis, we then demonstrate that IL-17RA can also bind to the "A-face" of IL-17A/F with similar affinity. Further, we show that IL-17RC does not discriminate between the two faces of the cytokine heterodimer either, thus enabling the formation of two topologically-distinct heterotrimeric complexes with potentially different signaling properties.
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