Interleukin-17 and its target genes: mechanisms of interleukin-17 function in disease

Authors

  • Reiko M. Onishi,

    1. Department of Medicine, Division of Rheumatology & Clinical Immunology, University of Pittsburgh, Pittsburgh PA
    2. Department of Oral Biology, University at Buffalo, State University of New York, Buffalo NY, USA
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  • Sarah L. Gaffen

    1. Department of Medicine, Division of Rheumatology & Clinical Immunology, University of Pittsburgh, Pittsburgh PA
    2. Department of Oral Biology, University at Buffalo, State University of New York, Buffalo NY, USA
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S. L. Gaffen, University of Pittsburgh, Division of Rheumatology & Clinical Immunology, S708 Biomedical Science Tower, 3500 Terrace Street, Pittsburgh PA 15261, USA. Email: sig65@pitt.edu
Senior author: Sarah L. Gaffen

Summary

Interleukin-17 (IL-17) has emerged as a central player in the mammalian immune system. Although this cytokine exerts a host-defensive role in many infectious diseases, it promotes inflammatory pathology in autoimmunity and other settings. A myriad of studies have focused on how IL-17-producing cells are generated. However, the means by which IL-17 achieves its effects, either for the benefit or the detriment of the host, are due in large part to the induction of new gene expression. Whereas many IL-17 target genes are common to different disease states, in some cases the effects of IL-17 differ depending on the target cell, infectious site or pathogen. Gene products induced by IL-17 include cytokines (IL-6, granulocyte-colony-stimulating factor, tumour necrosis factor-α), chemokines (CXCL1, CXCL2, CCL20, among many others), inflammatory effectors (acute-phase protesins, complement) and antimicrobial proteins (defensins, mucins). Different cell types appear to respond differently to IL-17 in terms of target gene expression, with notable differences seen in mesenchymal and epithelial cells compared with cells of haematopoietic origin. Here, we summarize the major IL-17 target genes that mediate this cytokine’s activities in both autoimmune and chronic diseases as well as during various types of infections.

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