Bridgewood, C, Newton, D orcid.org/0000-0002-0214-1486, Bragazzi, N orcid.org/0000-0001-8409-868X et al. (2 more authors) (2021) Unexpected connections of the IL-23/IL-17 and IL-4/IL-13 cytokine axes in inflammatory arthritis and enthesitis. Seminars in Immunology, 58. 101520. ISSN 1044-5323
Abstract
The IL-23/IL-17 cytokine axis is related to spondyloarthropathy (SpA) pattern diseases that target the skin, eye, gut and joints. These share overlapping target tissues with Th2 type or allergic diseases, including the skin, eye and gut but SpA diseases exhibit distinct microanatomical topography, molecular characteristics, and clinical features including uveitis, psoriasis, apical pulmonary involvement, lower gastrointestinal involvement with colitis, and related arthritides including psoriatic arthritis and ankylosing spondylitis. Inflammatory arthritis is conspicuously absent from the Th2 diseases which are characterised IL-4/IL-13 dependent pathway activation including allergic rhino-conjunctivitis, atopic eczema, allergic asthma and food allergies. This traditional understanding of non-overlap of musculoskeletal territory between that atopic diseases and the IL-17 -mediated SpA diseases is undergoing a critical reappraisal with the recent demonstration of IL-4/IL-13 blockade, may be associated with the development of SpA pattern arthritis, psoriasiform skin disease and occasional anterior uveitis. Given the known plasticity within Th paradigm pathways, these findings suggest dynamic Th2 cytokine and Th17 cytokine counter regulation in vivo in humans. Unexpected, this is the case in peripheral enthesis and when the IL-4/13 immunological brake on IL-23/17 cytokines is removed, a SpA phenotype may emerge. We discuss hitherto unexpected observations in SpA, showing counter regulation between the Th17 and Th2 pathways at sites including the entheses that collectively indicate that the emergent reverse translational therapeutic data is more than coincidental and offers new insights into the “Th paradigms” in atopy and SpA.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | Atopic Dermatitis; Dupilumab; Enthesis; IL-23; Psoriasis |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Experimental Musculoskeletal Medicine (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 04 Jan 2022 15:52 |
Last Modified: | 09 Jan 2023 16:57 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.smim.2021.101520 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:181742 |