Macleod, T, Bridgewood, C and McGonagle, D (2023) Role of neutrophil interleukin-23 in spondyloarthropathy spectrum disorders. The Lancet Rheumatology, 5 (1). e47-e57. ISSN 2665-9913
Abstract
Neutrophilic inflammation is a pervasive characteristic common to spondyloarthropathies and related disorders. This inflammation manifests as Munro's microabscesses of the skin and osteoarticular neutrophilic inflammation in patients with psoriatic arthritis, intestinal crypt abscesses in patients with inflammatory bowel disease, ocular hypopyon in anterior uveitis, and neutrophilic macroscopic and microscopic inflammation in patients with Behçet's disease. Strong MHC class I associations are seen in these diseases, which represent so-called MHC-I-opathies, and these associations indicate an involvement of CD8 T-cell immunopathology that is not yet well understood. In this Personal View, we highlight emerging data suggesting that the T-cell-neutrophil axis involves both a T-cell-mediated and interleukin (IL)-17-mediated (type 17) recruitment and activation of neutrophils, and also a sequestration of activated neutrophils at disease sites that might directly amplify type 17 T-cell responses. This amplification likely involves neutrophilic production of IL-23 and proteases as well as other feedback mechanisms that could be regulated by local microbiota, pathogens, or tissue damage. This crosstalk between innate and adaptive immunity offers a novel explanation for how bacterial and fungal microbes at barrier sites could innately control type 17 T-cell development, with the aim of restoring tissue homoeostasis, and could potentially explain features of clinical disease and treatment response, such as the fast-onset action of the IL-23 pathway blockade in certain patients. This axis could be crucial to understanding non-response to IL-23 inhibitors among patients with ankylosing spondylitis, as the axial skeleton is a site rich in neutrophils and a site of haematopoiesis with myelopoiesis in adults.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2022 Elsevier Ltd. All rights reserved. This is an author produced version of an article published in The Lancet Rheumatology. Uploaded in accordance with the publisher's self-archiving policy. |
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: | 03 Feb 2023 08:56 |
Last Modified: | 05 Mar 2024 13:30 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/s2665-9913(22)00334-4 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:195811 |
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