The role of IL-17A in axial spondyloarthritis and psoriatic arthritis: recent advances and controversies

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Abstract

Although the pathogenic mechanisms underlying axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) are not fully elucidated, several lines of evidence suggest that immune responses mediated by interleukin 17A (IL-17A) play a pivotal role in both diseases. This is best highlighted by the significant clinical efficacy shown with inhibitors of IL-17A in treating axSpA and PsA. Nevertheless, a number of knowledge gaps exist regarding the role of IL-17A in the pathophysiology of spondyloarthritis in man, including its cellular origin, its precise role in discrete disease processes such enthesitis, bone erosion, and bone formation, and the reasons for the discrepant responses to IL-17A inhibition observed in certain other spondyloarthritis manifestations. In this review, we focus on the latest data from studies investigating the role of IL-17A in ankylosing spondylitis (AS) and PsA that build on existing and emerging scientific knowledge in the field. Key remaining research questions are also highlighted to guide future research.

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Pain regulation by non-neuronal cells and inflammation

R.-R. Ji, A. Chamessian, Y.-Q. Zhang (2016)

Acute pain is protective and a cardinal feature of inflammation. Chronic pain after arthritis, nerve injury, cancer, and chemotherapy is associated with chronic neuroinflammation, a local inflammation in the peripheral or central nervous system. Accumulating evidence suggests that non-neuronal cells such as immune cells, glial cells, keratinocytes, cancer cells, and stem cells play active roles in the pathogenesis and resolution of pain. We review how non-neuronal cells interact with nociceptive neurons by secreting neuroactive signaling molecules that modulate pain. Recent studies also suggest that bacterial infections regulate pain through direct actions on sensory neurons, and specific receptors are present in nociceptors to detect danger signals from infections. We also discuss new therapeutic strategies to control neuroinflammation for the prevention and treatment of chronic pain.

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Requirement of Interleukin 17 Receptor Signaling for Lung Cxc Chemokine and Granulocyte Colony-Stimulating Factor Expression, Neutrophil Recruitment, and Host Defense

Lu-peng Ye, Fred H. Rodriguez, Suzanne Kanaly … (2001)

Bacterial pneumonia is an increasing complication of HIV infection and inversely correlates with the CD4+ lymphocyte count. Interleukin (IL)-17 is a cytokine produced principally by CD4+ T cells, which induces granulopoiesis via granulocyte colony-stimulating factor (G-CSF) production and induces CXC chemokines. We hypothesized that IL-17 receptor (IL-17R) signaling is critical for G-CSF and CXC chemokine production and lung host defenses. To test this, we used a model of Klebsiella pneumoniae lung infection in mice genetically deficient in IL-17R or in mice overexpressing a soluble IL-17R. IL-17R–deficient mice were exquisitely sensitive to intranasal K. pneumoniae with 100% mortality after 48 h compared with only 40% mortality in controls. IL-17R knockout (KO) mice displayed a significant delay in neutrophil recruitment into the alveolar space, and had greater dissemination of K. pneumoniae compared with control mice. This defect was associated with a significant reduction in steady-state levels of G-CSF and macrophage inflammatory protein (MIP)-2 mRNA and protein in the lung in response to the K. pneumoniae challenge in IL-17R KO mice. Thus, IL-17R signaling is critical for optimal production of G-CSF and MIP-2 and local control of pulmonary K. pneumoniae infection. These data support impaired IL-17R signaling as a potential mechanism by which deficiency of CD4 lymphocytes predisposes to bacterial pneumonia.

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Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity.

Anne Puel, Sophie Cypowyj, Jacinta Bustamante … (2011)

Chronic mucocutaneous candidiasis disease (CMCD) is characterized by recurrent or persistent infections of the skin, nails, and oral and genital mucosae caused by Candida albicans and, to a lesser extent, Staphylococcus aureus, in patients with no other infectious or autoimmune manifestations. We report two genetic etiologies of CMCD: autosomal recessive deficiency in the cytokine receptor, interleukin-17 receptor A (IL-17RA), and autosomal dominant deficiency of the cytokine interleukin-17F (IL-17F). IL-17RA deficiency is complete, abolishing cellular responses to IL-17A and IL-17F homo- and heterodimers. By contrast, IL-17F deficiency is partial, with mutant IL-17F-containing homo- and heterodimers displaying impaired, but not abolished, activity. These experiments of nature indicate that human IL-17A and IL-17F are essential for mucocutaneous immunity against C. albicans, but otherwise largely redundant.

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Author and article information

Journal

Journal ID (nlm-ta): Ann Rheum Dis

Journal ID (iso-abbrev): Ann. Rheum. Dis

Journal ID (hwp): annrheumdis

Journal ID (publisher-id): ard

Title: Annals of the Rheumatic Diseases

Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )

ISSN (Print): 0003-4967

ISSN (Electronic): 1468-2060

Publication date (Print): September 2019

Publication date (Electronic): 5 July 2019

Volume: 78

Issue: 9

Pages: 1167-1178

Affiliations

[1 ] departmentLeeds Institute of Rheumatic and Musculoskeletal Medicine , University of Leeds , Leeds, UK

[2 ] NIHR Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton, Leeds Teaching Hospital Trust , Leeds, UK

[3 ] departmentInstitute of Infection Immunity and Inflammation , University of Glasgow , Glasgow, UK

[4 ] Rheumatology Department, Guy's and Saint Thomas' NHS Foundation Trust , London, UK

[5 ] Kennedy Institute of Rheumatology, University of Oxford , Oxford, UK

[6 ] departmentNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences , University of Oxford , Oxford, UK

[7 ] departmentInstitute of Ageing and Chronic Disease , University of Liverpool , Liverpool, UK

[8 ] Department of Academic Rheumatology, Aintree University Hospital , Liverpool, UK

Author notes

[Correspondence to ] Dr Robert Moots, University of Liverpool Institute of Ageing and Chronic Disease, Liverpool, L9 7AL, UK; r.j.moots@ 123456liverpool.ac.uk

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Robert Moots http://orcid.org/0000-0001-7019-6211

Article

Publisher ID: annrheumdis-2019-215356

DOI: 10.1136/annrheumdis-2019-215356

PMC ID: 6788885

PubMed ID: 31278139

SO-VID: a8a97d92-136c-4312-b49b-2113bbfe7ee0

License:

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

History

Date received : 08 March 2019

Date revision received : 17 May 2019

Date accepted : 14 June 2019

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100008272, Novartis Pharmaceuticals Corporation;

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ScienceOpen disciplines: Immunology

Keywords: ankylosing spondylitis,inflammation,psoriatic arthritis,spondyloarthritis

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ScienceOpen disciplines: Immunology

Keywords: ankylosing spondylitis, inflammation, psoriatic arthritis, spondyloarthritis

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The role of IL-17A in axial spondyloarthritis and psoriatic arthritis: recent advances and controversies

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Most cited references 167

Pain regulation by non-neuronal cells and inflammation

Requirement of Interleukin 17 Receptor Signaling for Lung Cxc Chemokine and Granulocyte Colony-Stimulating Factor Expression, Neutrophil Recruitment, and Host Defense

Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity.

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